PDE4B inhibitor as well as pharmaceutical composition and application thereof

Abstract

The present disclosure provides a compound of formula H having excellent PDE4B inhibitory activity, and a pharmaceutical composition and use thereof. The compounds provided by the present disclosure are useful for the effective treatment of PDE4-related diseases and disorders, including but not limited to respiratory tract inflammatory diseases, inflammatory bowel diseases, arthritis diseases, skin inflammatory diseases, eye inflammatory diseases, and diseases or cancers of the peripheral or central nervous system. # imgabs0 #

Description

[0001] This application claims priority from the following prior applications: a Chinese invention patent application with the patent application number 202410144764.1 and the title "PDE4B Inhibitors and Their Pharmaceutical Compositions and Uses", filed with the China National Intellectual Property Administration on February 1, 2024; and a Chinese invention patent application with the patent application number 202410637006.3 and the title "PDE4B Inhibitors and Their Pharmaceutical Compositions and Uses", filed with the China National Intellectual Property Administration on May 21, 2024. The entire text of the above prior applications is incorporated into this application by reference. Technical Field

[0002] The present disclosure relates to PDE4B inhibitors and their pharmaceutical compositions and uses, belonging to the field of chemical drugs. Background Art

[0003] Fibrosis is a general term for a large class of diseases. It can occur in almost all human tissues. Tissues and organs with fibrotic lesions gradually lose their normal functions, seriously affecting the quality of life of patients and even endangering their lives. Taking pulmonary fibrosis as an example, the fibrotic tissue loses its original elasticity, making it increasingly difficult for the lungs to expand and contract during breathing. The vital capacity decreases accordingly, and the patient's activity ability will be severely weakened.

[0004] Idiopathic Pulmonary Fibrosis (IPF) is a progressive pulmonary fibrosis disease. The disease progression of this type of pulmonary fibrosis is relatively fast and may lead to the death of patients within a few years, even with a shorter survival period than many cancer patients. Due to the gradual aggravation of pulmonary fibrosis and the unpredictability of disease progression, IPF patients suffer from the "pain of being unable to breathe" that is difficult for ordinary people to imagine and may die of respiratory failure and / or heart failure at any time. At the same time, because the clinical manifestations of the vast majority of IPF patients are not typical, they are more likely to be misdiagnosed or missed diagnosed as chronic obstructive pulmonary disease, bronchial asthma or other pulmonary diseases. The median survival period of patients after being diagnosed with IPF is only 2.5 to 5 years.

[0005] In China, the European Union, the United States and Japan, IPF is defined as a rare disease, and there are approximately 3 million IPF patients worldwide. The disease mainly affects patients over 50 years old, with more males than females. There is no publicly available large-scale epidemiological research data on the incidence of IPF in China. Due to China's large population base, the disease burden caused by IPF to individuals, families, society and public health resources cannot be underestimated.

[0006] The PDE4 subfamily contains four subtypes (PDE4A, PDE4B, PDE4C, and PDE4D), and there are differences in tissue distribution among different subtypes: PDE4A is ubiquitously present and has relatively high expression in adipose tissue, brain, heart, and testis; PDE4B is also widely distributed, especially with high levels of expression in the lung, immune cells, brain, heart, and skeletal muscle; PDE4C is mainly expressed in the testis and other tissues, has low expression in the lung, and is not expressed in blood and immune cells; PDE4D is mainly expressed in the brain, immune cells, and skeletal muscle cells. Thus, it can be seen that the PDE4B subtype has a higher degree of expression in the lung compared to other subtypes. In vitro studies targeting PDE4B in pulmonary fibrosis have demonstrated the important role of inhibiting PDE4B in anti-inflammation and anti-fibrosis. Inhibiting PDE4B can lead to an increase in the intracellular cAMP level, subsequently activating protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC), reducing the synthesis and release of pro-inflammatory cytokines, and increasing the synthesis of anti-inflammatory cytokines.

[0007] Although preclinical evidence indicates that PDE4 inhibitors are associated with anti-inflammatory and anti-fibrotic effects and may reduce inflammation and fibrotic remodeling in lung diseases, many PDE4 inhibitors have gastrointestinal side effects due to differences in selectivity, resulting in the termination of clinical trials. Therefore, there is a need to develop PDE4B inhibitors that exhibit better selectivity and / or lower gastrointestinal side effects. Summary of the Invention

[0009] Regarding the above technical problems, the present disclosure provides a compound represented by the following formula H, its racemate, stereoisomer, tautomer, isotope-labeled substance, solvate, polymorph, metabolite, pharmaceutically acceptable salt, or prodrug:

[0010]

[0011] Wherein:

[0012] X1 represents a chemical bond, C 1-20 alkylene, O, S, NR q , S(=O), S(=O)2, or C(=O);

[0013] R q is selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), and the following groups that are unsubstituted or optionally substituted by 1, 2, or more R f : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 vinyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cyclenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocycloaryloxy, C 1-20 alkylthio, C 2-20 vinylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cyclenylthio, C 3-20 cycloalkylnylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocycloarylthio, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 , -C(O)OR 42 , -OC(O)R 43 , -S(O)2R 44 , -S(O)2OR 45 , -OS(O)2R 46 , -P(O)(OR 47 )(OR 48 );

[0014] L represents a chemical bond, C 2-20 alkynyl or Cy; wherein, L can be connected to X1 or R at any site c ;

[0015] Cy represents a 3-20 membered heterocyclic group, C 6-20 aryl, 5-20 membered heteroaryl, wherein the 3-20 membered heterocyclic group, C 6-20 aryl, 5-20 membered heteroaryl can optionally be fused with a 4-7 membered cycloalkyl group, provided that when the heterocyclic group contains an N atom, the heterocyclic group can be bonded to the carbon atom at the 2-position of the pyrimidine ring in formula H through its N atom or C atom;

[0016] W represents a chemical bond, CH, O, S, N, -S(O)-, -S(O)2-, -C(O), sub-C 1-6 alkyl, sub-C 2-6 alkenyl or sub-C 2-6 alkynyl;

[0017] R2 is selected from absent, H, unsubstituted or optionally substituted by one, two or more Rs d1 and the following groups: C 6-20 aryl, 5-20 membered heteroaryl;

[0018] R 2’ represents absent, H, halogen, OH, CN, unsubstituted or optionally substituted by one, two or more Rs d2 and the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2;

[0019] provided that R2 and R 2’ are not simultaneously "absent";

[0020] Alternatively, R2, R 2’ together with the atoms to which they are attached may form an unsubstituted or optionally substituted by one, two or more Rs d3 and the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, 6-20 membered aryl;

[0021] R a represents H or -X-R3;

[0022] X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0023] R3 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d4 substituted groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2;

[0024] R b represents H or -Y-R4;

[0025] Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0026] R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d5 substituted groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2;

[0027] provided that R a , R b are not both H at the same time;

[0028] Alternatively, R a , R b together with the atom to which it is attached form unsubstituted or optionally substituted by one, two or more R d6 substituted groups: C 5-20 cycloalkenyl, 3- to 20-membered heterocyclic group, 5- to 20-membered heteroaryl, 6- to 20-membered aryl;

[0029] Each R d1 , R d2 , R d3 , R d4 , R d5 , R d6 is the same or different and independently of one another is selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), SO, SO2, unsubstituted or optionally substituted by one, two or more R e substituted groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 Alkyl oxy, C 2-20 Alkenyl oxy, C 2-20 Alkynyl oxy, C 3-20 Cycloalkyl oxy, C 3-20 Cycloalkenyl oxy, C 3-20 Cycloalkynyl oxy, C 6-20 Aryl oxy, 5-20 membered heteroaryl oxy, 3-20 membered heterocyclic group oxy, C 1-20 Alkyl thio, C 2-20 Alkenyl thio, C 2-20 Alkynyl thio, C 3-20 Cycloalkyl thio, C 3-20 Cycloalkenyl thio, C 3-20 Cycloalkynyl thio, C 6-20 Aryl thio, 5-20 membered heteroaryl thio, 3-20 membered heterocyclic group thio, NH2, -C(O)R 31 、-CH2-C(O)R 31 、-C(O)OR 32 、-CH2C(O)OR 32 、-C(O)NHR 32 、-CH2C(O)NHR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 );

[0030] Alternatively, when there are two or more substituents selected from R d1 、R d2 、R d3 、R[[ID=II]] d4 、R d5 、R d6 on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R e substituted following groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group;

[0031] Each R c is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R eThe following substituted groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl-O-C 6-20 aryl-, 5-20 membered heteroaryl-N-C 6-20 aryl-, 5-20 membered heteroaryl-S-C 6-20 aryl-, 5-20 membered heteroaryl-CH2-C 6-20 aryl-, C 4-10 cycloalkyl fused to C 6-20 aryl-, 4-10 membered heterocycloalkyl fused to C 6-20 aryl-, 4-10 membered heterocycloalkenyl fused to C 6-20 aryl-, C 4-10 cycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkenyl-C 6-20 aryl-, 5-20 membered heteroaryl, C 4-10 cycloalkyl fused to 5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl fused to 5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl fused to 5-20 membered heteroaryl-, C 4-10 cycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryl-, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 31 、-C(O)OR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR35 、 -OS(O)2R 36 、 -P(O)(OR 37 )(OR 38 );

[0032] m is an integer selected from 1 to 10;

[0033] Each R e is the same or different and independently selected from H, halogen, OH, CN, NO2, NH2, oxo(=O), thioxo(=S), O-CONH2, O-CONHR f 、 unsubstituted or optionally substituted by 1, 2 or more Rs f of the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 、 -C(O)OR 42 、 -OC(O)R 43 、 -S(O)2R 44 、 -S(O)2OR 45 、 -OS(O)2R 46 、 -P(O)(OR 47 )(OR 48 );

[0034] Alternatively, when there are two or more substituents selected from R e on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f substituted group selected from the following: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group;

[0035] Each R f is the same or different and independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), an unsubstituted or optionally substituted by 1, 2 or more R g substituted group selected from the following: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 51 , -C(O)OR 52 , -OC(O)R 53 , -S(O)2R 54 , -S(O)2OR 55 , -OS(O)2R 56 , -P(O)(OR 57 )(OR 58 );

[0036] Alternatively, when there are two or more substituents selected from R fWhen there are substituents, the two substituents can together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more Rs g substituted with the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group;

[0037] Each R g is the same or different and independently of one another is selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2;

[0038] Each R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 is the same or different and independently of one another is selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2;

[0039] The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spiro ring), or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, for example, 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the states of nitrogen oxides, -S(O)- or -S(O)2-;

[0040] Said C 6-20 Aryl represents a monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a monoaromatic ring or a polyaromatic ring fused together;

[0041] The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic aromatic ring system, the aromatic ring system having 5 to 20 ring atoms and containing 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S.

[0042] According to a preferred embodiment of the context of the present disclosure, the compound does not include a compound selected from the following and / or its stereoisomers and / or its racemates:

[0043]

[0044] According to an embodiment of the present disclosure, the present disclosure provides a compound represented by the following formula G, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug:

[0045]

[0046] Wherein:

[0047] Cy represents a chemical bond, a 3- to 20-membered heterocyclic group, C 6-20 aryl, 5- to 20-membered heteroaryl, provided that when the heterocyclic group contains an N atom, the heterocyclic group can be bonded to the carbon atom at the 2-position of the pyrimidine ring in formula G through its N atom or C atom;

[0048] W represents a chemical bond, CH, O, S, N, -S(O)-, -S(O)2-, -C(O), sub-C 1-6 alkyl, sub-C 2-6 alkenyl or sub-C 2-6 alkynyl;

[0049] R2 is selected from absent, H, unsubstituted or optionally substituted by 1, 2 or more Rd1 The following substituted groups: C 6-20 Aryl, 5-20 membered heteroaryl;

[0050] R 2’ Represents absent, H, halogen, OH, CN, unsubstituted or optionally substituted by 1, 2 or more R d2 The following substituted groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 Alkoxy, C 2-20 Alkenyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2;

[0051] Provided that R2 and R 2’ Are not simultaneously "absent";

[0052] Or alternatively, R2, R 2’ May together with the atom to which it is attached form an unsubstituted or optionally substituted by 1, 2 or more R d3 The following substituted groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, 6-20 membered aryl;

[0053] R a Represents H or -X-R3;

[0054] X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0055] R3 represents H, halogen, OH, CN, -CH2CF3, -NHRd4 , unsubstituted or optionally substituted with 1, 2 or more R d4 Substituted with the following groups: C 1-20 Alkyl, -C(O)R 61 、-C(O)OR 62 、-OC(O)R 63 , NH2;

[0056] R b represents H or -Y-R4;

[0057] Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0058] R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted with 1, 2 or more R d5 Substituted with the following groups: C 1-20 Alkyl, -C(O)R 61 、-C(O)OR 62 、-OC(O)R 63 , NH2;

[0059] The condition is R a 、R b Not at the same time H;

[0060] Or, R a 、R b Together with the atoms to which it is attached, it forms an unsubstituted or optionally substituted group consisting of 1, 2 or more R d6 Substituted with the following groups: C 5-20 Cycloalkenyl, 3-20 membered heterocyclyl, 5-20 membered heteroaryl, 6-20 membered aryl;

[0061] Every R d1 、R d2 、R d3 、R d4 、R d5 、R d6 the same or different, independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), unsubstituted or optionally substituted with 1, 2 or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20Alkyloxy, C 2-20 Alkenyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5 - 20 - membered heteroaryloxy, 3 - 20 - membered heterocycloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5 - 20 - membered heteroarylthio, 3 - 20 - membered heterocyclothio, NH2, -C(O)R 31 , -CH2 - C(O)R 31 , -C(O)OR 32 , -CH2C(O)OR 32 , -C(O)NHR 32 , -CH2C(O)NHR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 );

[0062] Alternatively, when there are two or more substituents selected from R d1 , R d2 , R d3 , R d4 , R d5 , R d6 on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R e substituted following groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5 - 20 - membered heteroaryl, 3 - 20 - membered heterocyclic group;

[0063] Each R c is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), an unsubstituted or optionally substituted by 1, 2 or more R e substituted following groups: C 1-20 Alkyl, C2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5 - 20 membered heteroaryl, 3 - 20 membered heterocyclic group, C 1-20 Alkyl oxy, C 2-20 Alkenyl oxy, C 2-20 Alkynyl oxy, C 3-20 Cycloalkyl oxy, C 3-20 Cycloalkenyl oxy, C 3-20 Cycloalkynyl oxy, C 6-20 Aryl oxy, 5 - 20 membered heteroaryl oxy, 3 - 20 membered heterocyclic group oxy, C 1-20 Alkyl thio, C 2-20 Alkenyl thio, C 2-20 Alkynyl thio, C 3-20 Cycloalkyl thio, C 3-20 Cycloalkenyl thio, C 3-20 Cycloalkynyl thio, C 6-20 Aryl thio, 5 - 20 membered heteroaryl thio, 3 - 20 membered heterocyclic group thio, NH2, -C(O)R 31 , -C(O)OR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 );

[0064] m is an integer selected from 1 to 10;

[0065] Each R e is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R f substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5 - 20 membered heteroaryl, 3 - 20 membered heterocyclic group, C 1-20 Alkyl oxy, C 2-20 Alkenyl oxy, C 2-20 Alkynyl oxy, C 3-20 Cycloalkyl oxy, C 3-20Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocycloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclothio, NH2, -C(O)R 41 , -C(O)OR 42 , -OC(O)R 43 , -S(O)2R 44 , -S(O)2OR 45 , -OS(O)2R 46 , -P(O)(OR 47 )(OR 48 );

[0066] Or, when there are two or more substituents selected from R e on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f substituted following groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group;

[0067] Each R f is the same or different and independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), an unsubstituted or optionally substituted by 1, 2 or more R g substituted following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 Alkyl oxy, C 2-20 Alkenyl oxy, C 2-20 Alkynyl oxy, C 3-20 Cycloalkyl oxy, C 3-20 Cycloalkenyl oxy, C 3-20 Cycloalkynyl oxy, C 6-20Aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclyloxy, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclylthio, NH2, -C(O)R 51 , -C(O)OR 52 , -OC(O)R 53 , -S(O)2R 54 , -S(O)2OR 55 , -OS(O)2R 56 , -P(O)(OR 57 )(OR 58 );

[0068] Or, when there are two or more substituents selected from R f on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R g substituted the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclyl;

[0069] Each R g is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclyl, NH2;

[0070] Each R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 41 , R 42 , R 43 , R 44, R 45 , R 46 , R 47 , R 48 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 are the same or different and are each independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2;

[0071] The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spiro ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, for example 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the state of nitrogen oxide, -S(O)- or -S(O)2-;

[0072] The C 6-20 aryl represents a monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a monoaromatic ring or a polyaromatic ring fused together;

[0073] The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic aromatic ring system having 5 to 20 ring atoms and containing 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S.

[0074] According to an embodiment of the present invention, the cycloalkyl can be saturated or partially saturated.

[0075] According to an embodiment of the present invention, the compound represented by formula G, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug may be selected from the compounds represented by the following formula I, II, III, IV, V, VI, VII, VIII or IX, their racemates, stereoisomers, tautomers, isotope-labeled compounds, solvates, polymorphs, metabolites, pharmaceutically acceptable salts or prodrugs:

[0076]

[0077] The groups in the above formulas I to IX may independently have the definitions in the context of the present disclosure specification.

[0078] According to an embodiment of the present invention, the compound of formula I may have the following definitions:

[0079]

[0080] Wherein:

[0081] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0082] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0083] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0084] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0085] R1 represents hydrogen, a single- or poly-cyclic C 6-20 -aryl, which may be optionally and independently substituted at the ortho, para or meta positions by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 - cycloalkyl, C 1-3 - alkyl-(monocyclic or polycyclic - C 6-20 - aryl), 3 - 20 - membered heterocyclic - C 6-20 - aryl, 3 - 20 - membered heterocycle, C 1-6 - alkyl, C 1-3 - fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl - C 1-6 - alkyl, 3 - 20 - membered heterocyclic - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6- alkyl, C 6-20- aryl, SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 1.2 R 1.3 substituted by substituents of, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 - alkyl, C 6-20- aryl and NR 1.2 R 1.3 ;

[0086] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 - alkyl - OR 1.1 , SR 1.1 , C 1-3 - alkyl - SR 1.1 , SO - R 1.1 , C 1-3 - alkyl - SOR 1.1 , SO2 - R 1.1 , C 1-3 - alkyl - SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO - NR 1.1 CH2CO - NR 1.1 , CH2CH2CO - NR 1.1 , CH=CHCO - NR 1.1 , COR1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 2.3 ;

[0087] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0088] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0089] Cycloalkyl may be saturated or partially saturated;

[0090] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, monocyclic or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C6-20- substituted with an aryl substituent,

[0091] R 1.2 and R 1.3 independently represent H or selected from C 1-6- Alkyl, mono- or bicyclic C 3-10- Cycloalkyl, C 6-20- Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, mono- or bicyclic C 6-20- Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20- Aryl and COOR 1.1 substituted with a substituent, or

[0092] R2 represents hydrogen, a mono- or polycyclic C 6-20- Aryl may be substituted at the ortho, para or meta position by one, two or three fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 2.1 ,COOR 2.1 CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,NR 2.2 R 2.3 ,CH2-NR 2.2 R 2.3 ,CH2CH2-NR 2.2 R 2.3 ,C 3-10 -cycloalkyl, 3-20 membered heterocyclic ring, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- Aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, C6-20- aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 in the group.

[0093] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may be optionally and independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 , 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20-(aryl), 3- to 20-membered heterocyclic group-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted by substituents of, each of which substituents may optionally be further substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 ; one, two or more of the substituents selected from among

[0094] The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0095] The heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0096] The cycloalkyl may be saturated or partially saturated;

[0097] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl substituents;

[0098] R 2.2 and R 2.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20Aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 , or

[0099] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0100] Alternatively, R2 and R 2’ together with the atoms to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by one, two or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 ,SO-R 2.1 ,C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 ,C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-20- aryl, C 1-6 , -alkyl, C 6-20- aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ;

[0101] R3 represents H, C 1-6 , -alkyl, F, chlorine, bromine, hydroxyl, -CN, -CH2CN, -CH2COOR, -COOR, -CO-NH(CH3)C 1-3 , -fluoroalkyl, (C 1-6 , -alkyl)-OH, (C 1-6 , -alkyl)-OCH3, (C 1-6 , -alkyl)-NH2, (C 1-6 , -alkyl)-N(C 1-3 , -alkyl) or (C 1-6 , -alkyl)-NH;

[0102] R 3’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 , -alkyl, C 5-10 , -heteroaryl-C 1-6 , -alkyl, C 3-10 , -heterocycle and C 5-10-heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; said groups may each optionally be substituted by one, two or more groups selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0103] Alternatively, R3 and R 3’ together represent oxo, methylene, ethylene and propylene, which may optionally be substituted by substituents selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2 and O-(C 1-3 -alkyl);

[0104] R4 represents H, C 1-6 -alkyl, F, chlorine, bromine, hydroxy, -CN, -CH2CN, -CH2COOR, -COOR, -CO-NH(CH3)C 1-3 -fluoroalkyl, (C 1-6 -alkyl)-OH, (C 1-6 -alkyl)-OCH3, (C 1-6 -alkyl)-NH2, (C 1-6 -alkyl)-N(C 1-3 -alkyl) or (C 1-6 -alkyl)-NH;

[0105] R 4’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; said groups may each optionally be substituted by one, two or more groups selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0106] Alternatively, R4 and R4’ collectively represent oxo, methylene, ethylene, and propylene, which may optionally be substituted with substituents selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3- alkyl);

[0107] R5 and R6 independently represent H, F, C 1-6 -alkyl, C 1-3 -fluoroalkyl, C 1-6 -alkyl-OH, C 1-6 -alkenyl-OCH3, C 1-6 -alkyl-NH2, C 1-6 -alkynyl-NH(C 1-3 -alkyl), and C 1-6 -alkyl-N(C 1-3 -alkyl)2;

[0108] Alternatively, R1 and R3 together with the C- and N-atoms of piperidine form a saturated or partially saturated 5- or 7-membered heterocyclic group containing two or three nitrogen atoms, which may optionally be substituted with groups selected from -CH3, -CH2CH3, -CH2CH2CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3- alkyl);

[0109] Alternatively, R3 and R6 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with groups selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl);

[0110] Alternatively, R3 and R5 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with groups selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl);

[0111] Alternatively, R3 and R4 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl);

[0112] Alternatively, R4 and R6 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl);

[0113] Alternatively, R4 and R7 together with the carbon atom to which they are attached form a double bond.

[0114] According to an embodiment of the present invention, examples of R1 may be selected from the following groups:

[0115]

[0116]

[0117] According to an embodiment of the present invention, examples of -W-R2R 2’ may be selected from the following groups:

[0118]

[0119]

[0120]

[0121]

[0122]

[0123] According to an embodiment of the present invention, the compound of formula II has the following definitions:

[0124]

[0125] W represents CH, O, S, N, S(O), S(O)2, or C(O), C 1-2 -alkyl, vinyl, or ethynyl;

[0126] X represents CH2, O, S, NH, S(O), S(O)2, or C(O);

[0127] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0128] R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, which may be substituted at the ortho, para or meta position by one, two or three fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2 substituents, or by one, two or more substituents selected from OR 1.1 ,COOR 1.1 CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,NR 1.2 R 1.3 ,CH2-NR 1.2 R 1.3 ,CH2CH2-NR 1.2 R 1.3 ,C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic C 6-20- aryl), 3-20 membered heterocyclyl-C 6-20- Aryl, 3-20 membered heterocyclic ring, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- Aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, C 6-20- Aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by a substituent, each of which may be optionally substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- Aryl and NR 1.2 R 1.3 substituted by a substituent in

[0129] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ;

[0130] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0131] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group comprising 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0132] Cycloalkyl groups may be saturated or partially saturated;

[0133] R 1.1 Is H or selected from C 1-6- Alkyl, C 1-6- Alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- Aryl, 5-20 membered heteroaryl and heterocyclic ring, which may be optionally substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- Alkyl and C 5-10 substituted with an aryl substituent;

[0134] R 1.2 and R 1.3 independently represent H or selected from C 1-6- Alkyl, mono- or bicyclic C 3-10- Cycloalkyl, C 6-20- Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, mono- or bicyclic C 6-20- Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20- Aryl and COOR 1.1 Substituents substituted;

[0135] R2 represents hydrogen, a mono- or polycyclic C 6-20-An aryl group, which may optionally be independently substituted at the ortho, para or meta position by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 - cycloalkyl, 3 - 20 membered heterocycle, C 1-6 - alkyl, C 1-3 - fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl - C 1-6 - alkyl, 3 - 20 membered heterocycle - C 1-6 - alkyl, 5 - 20 membered heteroaryl - C 1-6- alkyl, C 6-20- aryl, C 1-3 - alkyl - SOR 2.1 , C 1-3 - alkyl - SO2R 2.1 , SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 2.2 R 2.3 and is substituted by substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 - alkyl, C 6-10- aryl and NR 2.2 R 2.3 ;

[0136] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 - alkyl - OR 2.1 , SR 2.1 , C1-3 -alkyl-SR 2.1 ,SO-R 2.1 ,C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 ,C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 is substituted by substituents of, and each of said substituents may optionally be substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 one, two or more substituents of;

[0137] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0138] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0139] Cycloalkyl may be saturated or partially saturated;

[0140] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl substituents;

[0141] R 2.2 and R 2.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 5-10 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocyclic, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 of the substituents, or

[0142] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocyclic and C 5-10 -heterocyclic, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups in each case may optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C1-6- alkyl and O-C 1-6- substituted by substituents of the alkyl group.

[0143] Alternatively,

[0144] R2 and R 2’ together form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O,

[0145] R3 represents a group selected from aryl and heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or is independently optionally substituted by 1, 2 or more groups selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 , -alkyl alcohol, monocyclic or bicyclic C 3-10 , -cycloalkyl, C 6-20- , aryl, C 1-6 , -alkyl, C 6-20- , aryl-C 1-6 , -alkyl, 5- to 20-membered heteroaryl-C 1-6- , alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 , -aryl), 3- to 20-membered heterocyclic-C 6-20 , -aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3substituted by substituents, each of which may optionally be substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- -alkyl, C 6-20- -aryl and NR 1.2 R 2.3 substituted by one, two or more substituents selected from;

[0146] R4 represents a group selected from aryl and heteroaryl, each of which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or each is independently optionally substituted by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- -aryl), 3-20 membered heterocyclic-C 6-20- -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted by substituents, each of which may optionally be substituted by OH, OR 2.1, oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 2.3 substituted by one, two or more substituents selected from the group consisting of;

[0147] The A ring represents a chemical bond, a single- or polycyclic C 6-20- aryl, which may be independently optionally substituted at the ortho, para or meta positions with one, two or three substituents independently selected from fluorine, chlorine, bromine, hydroxy, CN, NH2, or substituted by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 selected from the group consisting of; or,

[0148] Ring A represents a group selected from heterocycles or heteroaryls, each of which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and is further optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 1.3 ;

[0149] A heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0150] A heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0151] A cycloalkyl can be saturated or partially saturated;

[0152] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C<\ 1-10- alkyl and C 6-20- aryl;

[0153] R 1.2 and R 1.3 each independently represent H or a group selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20- aryl, 3- to 20-membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and which may optionally be substituted with one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ;

[0154] According to an embodiment of the present invention, examples of the A ring can be selected from the following groups:

[0155]

[0156]

[0157] According to an embodiment of the present invention, -W-R2R 2’ Examples may be selected from the following groups:

[0158]

[0159]

[0160]

[0161]

[0162] According to an embodiment of the present invention, examples of the -X-R3 substituent may be selected from the following groups:

[0163]

[0164]

[0165] According to an embodiment of the present invention, the compound of formula III has the following definitions:

[0166]

[0167] Wherein:

[0168] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0169] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0170] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0171] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0172] R1 represents hydrogen, a single- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions, optionally substituted by one, two or three substituents of fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,NR 1.2 R 1.3 ,CH2-NR 1.2 R 1.3 ,CH2CH2-NR 1.2 R 1.3 ,C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic -C 6-20- aryl), 3 - 20 membered heterocyclic -C 6-20- aryl, 3 - 20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl -C 1-6 -alkyl, 3 - 20 membered heterocyclic -C 1-6 -alkyl, 5 - 20 membered heteroaryl -C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents of, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 among the substituents,

[0173] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 ,C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 ,C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1, CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ;

[0174] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0175] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0176] Cycloalkyl may be saturated or partially saturated;

[0177] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 , -haloalkyl, mono- or bicyclic, -C 3-10 , -cycloalkyl, C 6-20 aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6-alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0178] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 , or

[0179] R2 represents hydrogen, a mono- or polycyclic C 6-20 aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three substituents of fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, C1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 2.2 R 2.3 among others,

[0180] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 ,SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 aryl, C 1-6 -alkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 is substituted by substituents of, each of which may optionally be substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 one, two or more substituents in;

[0181] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0182] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally related heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0183] Cycloalkyl may be saturated or partially saturated;

[0184] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, monocyclic or bicyclic C C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C6-20 substituted by an aryl substituent;

[0185] R 2.2 and R 2.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 or

[0186] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups in each case may optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0187] Alternatively, R2 and R 2’ together with the atom to which they are attached form a 4-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by one, two or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 、C 1-3-alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ;

[0188] Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by 1, 2 or more groups selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1, CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 , - cycloalkyl, C 1-3 , - alkyl - (monocyclic or polycyclic - C 6-20 aryl), 3 - 20 - membered heterocyclic - C 6-20 aryl, 3 - 20 - membered heterocycle, C 1-6 , - alkyl, C 1-3 , - fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl - C 1-6 , - alkyl, 3 - 20 - membered heterocyclic - C 1-6 , - alkyl, 5 - 20 - membered heteroaryl - C 1-6- alkyl, C 6-10 , - aryl, SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 1.2 R 1.3 substituted by substituents of, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 , - alkyl, C 6-20 aryl and NR 1.2 R 1.3 ;

[0189] Ring A represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 , - alkyl - OR 1.1 , SR 1.1 , C 1-3 , - alkyl - SR 1.1 , SO - R 1.1 , C 1-3 , - alkyl - SOR 1.1 , SO2 - R 1.1 , C 1-3 , - alkyl - SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1, CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 aryl, C 1-6 -alkyl, C C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, each of which may optionally be substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20 aryl and NR 1.2 R 1.3 ;

[0190] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0191] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0192] Cycloalkyl may be saturated or partially saturated;

[0193] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C1-6 - alkyl, mono - or bicyclic C 6-20 aryl, 5 - 20 - membered heteroaryl and heterocycle, which may optionally be selected from OH, O-(C 1-3 - alkyl), halogen, C 1-10- alkyl and C 6-20 aryl;

[0194] R 1.2 and R 1.3 independently of one another represent H or are selected from C 1-6- alkyl, mono - or bicyclic C 3-10- cycloalkyl, C 6-20 aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6 alkylene, mono - or bicyclic C 6-20 aryl, 3 - 20 - membered heterocycle, heteroaromatic ring, CO - NH2, CO - NH - CH3, - CO - N(CH3)2, SO2-(C 1-3 - alkyl), CO - R 1.1 and COOR 1.1 and the groups may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 - alkyl, C 6-20 aryl and COOR 1.1 .

[0195] Alternatively, according to an embodiment of the present invention,

[0196] According to an embodiment of the present invention, examples of the A ring may be selected from the following groups:

[0197]

[0198]

[0199] According to an embodiment of the present invention, examples of - W - R2R 2’ may be selected from the following groups:

[0200]

[0201]

[0202]

[0203]

[0204] According to an embodiment of the present invention, the compound of formula IV has the following definition:

[0205]

[0206] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0207] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0208] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0209] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0210] V represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0211] R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20 aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R1.3 is substituted by substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20 -aryl and NR 1.2 R 1.3 in the substituents,

[0212] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may be optionally and independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 -aryl, C 1-6 -alkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3substituted by substituents, and each of said substituents may optionally be substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20 aryl and NR 1.2 R 2.3 ;

[0213] Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0214] Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0215] Cycloalkyl may be saturated or partially saturated;

[0216] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0217] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 ; or

[0218] R2 represents hydrogen, a mono- or polycyclic C 6-20 aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, a 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, a 3- to 20-membered heterocycle-C 1-6 -alkyl, a 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 ; each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0219] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ;

[0220] Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0221] Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0222] Cycloalkyl may be saturated or partially saturated;

[0223] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0224] R 2.2 and R 2.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 2.1 or

[0225] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6-Alkenyl, C 2-6- Alkynyl, C 6-10- Aryl, C 6-10 -Aryl-C 1-6 -Alkyl, C 5-10 -Heteroaryl-C 1-6 -Alkyl, C 3-10 -Heterocycle and C 5-10 -Heterocycle, -NR’R”, Fluorine, C 1-6- Fluoroalkyl and C 1-6- Fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- Alkyl; the group may in each case optionally be substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- Alkyl and O-C 1-6- Alkyl and is substituted.

[0226] Alternatively, R2 and R 2’ together with the atom to which it is attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -Alkyl-OR 2.1 , SR 2.1 , C 1-3 -Alkyl-SR 2.1 ,SO-R 2.1 , C 1-3 -Alkyl-SOR 2.1 ,SO2-R 2.1 , C 1-3 -Alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 , C 1-6 -Alkyl alcohol, mono- or bicyclic C 3-10 -Cycloalkyl, C 6-20- Aryl, C 1-6 -Alkyl, C 6-20- Aryl-C1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroarylC 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ;

[0227] The A ring represents a chemical bond, a single- or polycyclic C 6-20 aryl, which may be independently optionally substituted at the ortho, para or meta positions each by one, two, or three independent groups selected from fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3- to 20-membered heterocyclic-C 6-20 aryl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C, 6-10 aryl-C 1-6 -alkyl, 3- to 20-membered heterocyclic-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents selected from OH, OR1.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- -aryl and NR 1.2 R 1.3 is substituted by a substituent selected from the group consisting of, or

[0228] Ring A represents a group selected from heterocycles or heteroaryl groups, each of which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, monocyclic or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by a substituent selected from the group consisting of OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6-alkyl, C 6-10- aryl and NR 1.2 R 1.3 are substituted by one, two or more substituents selected from;

[0229] heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0230] heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0231] cycloalkyl may be saturated or partially saturated;

[0232] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by one or more substituents selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl;

[0233] R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR1.1 substituted by substituents

[0234] According to an embodiment of the present invention, examples of the A ring may be selected from the following groups:

[0235]

[0236]

[0237] According to an embodiment of the present invention, -W-R2R 2’ Examples may be selected from the following groups:

[0238]

[0239]

[0240]

[0241]

[0242] According to an embodiment of the present invention, the compound of formula V has the following definitions:

[0243]

[0244] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0245] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0246] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0247] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0248] V represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0249] R1 represents hydrogen, a mono- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions, optionally substituted by one, two or three substituents of fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,NR 1.2 R 1.3 ,CH2-NR 1.2 R 1.3 ,CH2CH2-NR 1.2 R 1.3 ,C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic -C 6-20 aryl), 3-20 membered heterocyclic group -C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic -C 1-6 -alkyl, 5-20 membered heteroaryl -C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 is substituted by the substituents of, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0250] Or,

[0251] R1 represents a group selected from heterocycles and heteroaryls, which may be optionally and independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1, CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of 2.1 , oxygen, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 one, two or more substituents selected from;

[0252] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0253] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0254] Cycloalkyl may be saturated or partially saturated;

[0255] wherein R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 Aryl, 5-20 membered heteroaryl and heterocyclic ring, which may be optionally substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- Alkyl and C 6-20 substituted with an aryl substituent;

[0256] R 1.2 and R 1.3 independently represent H or selected from C 1-6- Alkyl, mono- or bicyclic C 3-10- Cycloalkyl, C 6-20 Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, mono- or bicyclic C 6-20 Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20- Aryl and COOR 1.1 substituted with a substituent, or

[0257] R2 represents hydrogen, a mono- or polycyclic C 6-20 Aryl may be substituted at the ortho, para or meta position by one, two or three fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 2.1 ,COOR 2.1 CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,NR 2.2 R 2.3 ,CH2-NR 2.2 R 2.3 ,CH2CH2-NR 2.2 R 2.3 ,C3-10 -cycloalkyl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 is substituted by substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 in the substituents,

[0258] Or,

[0259] R2 represents a group selected from heterocycles and heteroaryls, which may be optionally and independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 ,SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR2.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 Alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclyl-C 6-20 -aryl, 3-20 membered heterocyclic ring, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted by a substituent, each of which may be optionally substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- Alkyl, C 6-10- Aryl and NR 2.2 R 2.3 substituted by 1, 2 or more substituents;

[0260] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0261] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group comprising 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0262] Cycloalkyl groups may be saturated or partially saturated;

[0263] where R 2.1 Is H or selected from C 1-6- Alkyl, C 1-6- Alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic ring, which may be optionally substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- Alkyl and C 6-20substituted by an aryl substituent,

[0264] R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the group may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 or

[0265] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; and the group in each case may optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0266] Alternatively,

[0267] R2 and R 2’ together form a 4-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O,

[0268] The A ring represents a chemical bond, a mono- or polycyclic C 6-20-aryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 , C-cycloalkyl, C 1-3 , C-alkyl-(monocyclic or polycyclic-C 6-20 , 3-20 membered heterocyclic-C 6-20 , aryl, 3-20 membered heterocycle, C 1-6 , C-alkyl, C 1-3 , C-fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 , 3-20 membered heterocyclic-C 1-6 , 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 , aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and the substituents may each be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 , C-alkyl, C 6-10- aryl and NR 1.2 R 1.3 in turn, or,

[0269] Ring A represents a group selected from a heterocycle or heteroaryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 , C-alkyl-OR 1.1 , SR 1.1 , C 1-3-alkyl-SR 1.1 ,SO-R 1.1 ,C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 ,C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, each of which may optionally be substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0270] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0271] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0272] Cycloalkyl may be saturated or partially saturated;

[0273] R 1.1 Is H or selected from C 1-6- Alkyl, C 1-6- Alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic ring, which may be optionally selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- Alkyl and C 6-20 Aryl,

[0274] R 1.2 and R 1.3 independently represent H or selected from C 1-6- Alkyl, mono- or bicyclic C 3-10- Cycloalkyl, C 6-20 Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 Alkylene, mono- or bicyclic C 6-20 Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20 Aryl and COOR 1.1 substituted by a substituent.

[0275] According to an embodiment of the present invention, examples of Ring A may be selected from the following groups:

[0276]

[0277]

[0278] According to an embodiment of the present invention, -W-R2R 2’ Examples of substituents may be selected from the following groups:

[0279]

[0280]

[0281]

[0282]

[0283] According to an embodiment of the present invention, the compound of formula VI has the following definitions:

[0284]

[0285] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0286] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0287] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0288] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0289] R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C1-6 -alkyl, 3- to 20-membered heterocyclic-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 is substituted by substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 in the substituents,

[0290] Or,

[0291] R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3-alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted by substituents of, each of said substituents being optionally further substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ;

[0292] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0293] Heteroaryl ring is a s-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0294] Cycloalkyl may be saturated or partially saturated;

[0295] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may be optionally substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0296] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6-Alkyl, mono- or bicyclic C 6-20- Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20- Aryl and COOR 1.1 substituted with a substituent, or

[0297] R2 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, which may be substituted at the ortho, para or meta position by one, two or three fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2 substituents, or by one, two or more substituents selected from OR 2.1 ,COOR 2.1 CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,NR 2.2 R 2.3 ,CH2-NR 2.2 R 2.3 ,CH2CH2-NR 2.2 R 2.3 ,C 3-10 -cycloalkyl, 3-20 membered heterocyclic ring, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 Aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 、C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted by a substituent, each of which may be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1, oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 substituted by the substituents in;

[0298] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by 1, 2 or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted by the substituents, and each of said substituents may optionally be substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C6-10- Aryl and NR 2.2 R 2.3 are substituted by one, two or more substituents selected from the group consisting of;

[0299] Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0300] Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0301] Cycloalkyl may be saturated or partially saturated;

[0302] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0303] R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1substituted by a substituent;

[0304] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the group may in each case be optionally substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0305] Alternatively, R2 and R 2’ together with the atom to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 ,SO-R 2.1 ,C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 ,C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 ,C 1-6-alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ;

[0306] The A ring represents a chemical bond, a mono- or polycyclic C 6-20 aryl, which may be independently optionally substituted at the ortho, para or meta positions with one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxyl, CN, NH2, or with one, two or more groups selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10-aryl, SO2-CH3, SO2-CH2CH3, and SO2-NR 1.2 R 1.3 substituted by substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- -aryl, and NR 1.2 R 1.3 ; or,

[0307] The A ring represents a group selected from heterocycles or heteroaryls, each of which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, monocyclic or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR1.2 R 1.3 is substituted with substituents, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0308] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0309] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0310] Cycloalkyl may be saturated or partially saturated;

[0311] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl;

[0312] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R1.1 and COOR 1.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 .

[0313] According to an embodiment of the present invention, examples of the A ring may be selected from the following groups:

[0314]

[0315] According to an embodiment of the present invention, examples of the -W-R2R 2’ substituents may be selected from the following groups:

[0316]

[0317]

[0318]

[0319]

[0320] According to an embodiment of the present invention, the compound of formula VII has the following definitions:

[0321]

[0322] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0323] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0324] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0325] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0326] R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1, CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 - cycloalkyl, C 1-3 - alkyl-(monocyclic or polycyclic - C 6-20 - aryl), 3 - 20 - membered heterocyclic group - C 6-20 - aryl, 3 - 20 - membered heterocycle, C 1-6 - alkyl, C 1-3 - fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl - C 1-6 - alkyl, 3 - 20 - membered heterocyclic - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6- alkyl, C 6-10 - aryl, SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 1.2 R 1.3 substituted by the substituents of, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6 - alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0327] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 - alkyl - OR 1.1 , SR 1.1 , C 1-3 - alkyl - SR 1.1 , SO - R 1.1 , C 1-3 - alkyl - SOR 1.1 , SO2 - R 1.1 , C 1-3 - alkyl - SO2R 1.1 , COOR 1.1 , CH2COOR1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 - alkyl alcohol, mono - or bicyclic C 3-10 - cycloalkyl, C 6-10 - aryl, C 1-6 - alkyl, C 6-10 - aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6 alkyl, C 1-3 - alkyl - (monocyclic or polycyclic - C 6-20 - aryl), 3 - 20 - membered heterocyclic - C 6-20 - aryl, 3 - 20 - membered heterocycle, 5 - 20 - membered heteroaryl C 1-3 - alkyl - OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, and each of said substituents may optionally be substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ;

[0328] Heterocycle represents a 3 - 11 - membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0329] Heteroaryl ring is a 5 - 10 - membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0330] Cycloalkyl may be saturated or partially saturated;

[0331] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 - haloalkyl, mono - or bicyclic, - C 3-10 - cycloalkyl, C 6-20 aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C1-6 -alkyl, 3- to 20-membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0332] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3- to 20-membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and are optionally substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ;

[0333] R2 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic -C 6-20 -aryl), 3-20 membered heterocyclic -C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl -C 1-6 -alkyl, 3-20 membered heterocyclic -C 1-6 -alkyl, 5-20 membered heteroaryl -C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl -SOR 2.1 , C 1-3 -alkyl -SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted by substituents of, each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 among,

[0334] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl -OR 2.1 , SR 2.1 , C 1-3 -alkyl -SR 2.1 , SO-R 2.1 , C 1-3 -alkyl -SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl -SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1, CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 is substituted by substituents of, and each of said substituents may optionally be substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ;

[0335] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0336] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0337] Cycloalkyl may be saturated or partially saturated;

[0338] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0339] R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 or

[0340] R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0341] Alternatively, R2 and R 2’ together with the atoms to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by one, two or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C1-3 -alkyl-SR 2.1 ,SO-R 2.1 ,C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 ,C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 ,NR 2.2 R 2.3 ,C 6-20- aryl and NR 2.2 R 2.3 ;

[0342] Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions each by one, two, or three independent groups selected from fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by 1, 2 or more groups selected from OR 1.1 ,COOR 1.1 CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1, NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 - cycloalkyl, C 1-3 - alkyl-(monocyclic or polycyclic - C 6-20 - aryl), 3 - 20 membered heterocyclic group - C 6-20 - aryl, 3 - 20 membered heterocycle, C 1-6 - alkyl, C 1-3 - fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl - C 1-6 - alkyl, 3 - 20 membered heterocyclic - C 1-6 - alkyl, 5 - 20 membered heteroaryl - C 1-6- alkyl, C 6-10 - aryl, SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 1.2 R 1.3 substituted by the substituents of, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 - alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; or,

[0343] Ring A represents a group selected from heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 - alkyl - OR 1.1 , SR 1.1 , C 1-3 - alkyl - SR 1.1 , SO - R 1.1 , C 1-3 - alkyl - SOR 1.1 , SO2 - R 1.1 , C 1-3 - alkyl - SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO - NR 1.1 CH2CO - NR 1.1, CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0344] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0345] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0346] Cycloalkyl may be saturated or partially saturated;

[0347] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, monocyclic or bicyclic C 6-20-aryl, 5- to 20-membered heteroaryl, and heterocycle, which may optionally be selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl, and C 6-20 aryl;

[0348] R 1.2 and R 1.3 each independently represent H or a group selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkylene, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 , which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl, and COOR 1.1 .

[0349] According to an embodiment of the present invention, examples of the A ring may be selected from the following groups:

[0350]

[0351] According to an embodiment of the present invention, examples of the -W-R2R 2’ group may be selected from the following groups:

[0352]

[0353]

[0354]

[0355]

[0356] According to an embodiment of the present invention, the compound of formula VIII has the following definition:

[0357]

[0358] W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl;

[0359] X represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0360] Y represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0361] Z represents CH2, O, S, NH, S(O), S(O)2 or C(O);

[0362] R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituents, each of said substituents optionally further substituted by 1, 2 or more substituents selected from OH, OR 1.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R1.3 substituted by the substituents in

[0363] Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR

[0364] The heterocyclic ring represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0365] The heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0366] The cycloalkyl group can be saturated or partially saturated;

[0367] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5- to 20-membered heteroaryl and heterocyclic ring, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents;

[0368] R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocyclic ring, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups thereof may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ;

[0369] R2 represents hydrogen, a mono- or polycyclic C 6-20-aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted, and each of said substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 in the group,

[0370] Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally and independently at the ortho, para or meta positions be substituted by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by 1, 2 or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C1-3 -alkyl-SR 2.1 ,SO-R 2.1 ,C 1-3 -alkyl-SOR 2.1 ,SO2-R 2.1 ,C 1-3 -alkyl-SO2R 2.1 ,COOR 2.1 ,CH2COOR 2.1 ,CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted by substituents of, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ;

[0371] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0372] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0373] Cycloalkyl may be saturated or partially saturated;

[0374] R 2.1 Is H or selected from C 1-6- Alkyl, C 1-6- Alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 Aryl, 5-20 membered heteroaryl and heterocyclic ring, which may be optionally substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- Alkyl and C 6-20 substituted with an aryl substituent;

[0375] R 2.2 and R 2.3 independently represent H or selected from C 1-6- Alkyl, mono- or bicyclic C 3-10- Cycloalkyl, C 6-20 Aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, mono- or bicyclic C 6-20- Aryl, 3-20 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3、-CO-N(CH3)2、SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 A group, which may be optionally substituted by 1, 2 or more selected from OH, halogen, C 1-6 -alkyl, C 6-20- Aryl and COOR 2.1 Substituents substituted;

[0376] R 2’ Indicates H, F, Me, C 1-6- Alkyl, C 2-6- Alkenyl, C 2-6- Alkynyl, C 6-10- Aryl, C 6-10 -Aryl-C 1-6 -alkyl, C 6-20 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocyclic and C 6-20 -heterocycle, -NR'R", fluorine, C 1-6- Fluoroalkyl and C 1-6-Fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; said groups may each optionally be substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl.

[0377] Alternatively, R2 and R 2’ together with the atom to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, monocyclic or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3, C 6-20- aryl and NR 2.2 R 2.3 ;

[0378] R4 represents a group selected from aryl and heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or independently optionally substituted by 1, 2 or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituents, and each of said substituents may optionally be further substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3substituted by one, two or more of the substituents;

[0379] The A ring represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta position by one, two or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; or,

[0380] The A ring represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 are substituted by substituents of, each of which may optionally be substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ;

[0381] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0382] A heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0383] A cycloalkyl may be saturated or partially saturated;

[0384] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted with one or more substituents selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl;

[0385] R 1.2 and R 1.3 each independently represent H or a group selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3- to 20-membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and which may optionally be substituted with one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ;

[0386] According to an embodiment of the present invention, examples of the A ring may be selected from the following groups:

[0387]

[0388] According to an embodiment of the present invention, examples of the -W-R2R 2’ group may be selected from the following groups:

[0389]

[0390]

[0391]

[0392]

[0393]

[0394] According to an embodiment of the present invention, the compound of formula IX has the following definition:

[0395]

[0396] Wherein:

[0397] X1 represents a chemical bond, C 1-20 alkylene, O, S, NR q , S(=O), S(=O)2 or C(=O);

[0398] U represents -(CH2) t -, O, S, NR q , S(=O), S(=O)2 or C(=O), where t represents 0, 1, 2 or 3;

[0399] R q is selected from H, halogen, OH, CN, NO2, NH2, oxo(=O), thioxo(=S), the following groups which are unsubstituted or optionally substituted by 1, 2 or more R f substituents: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5-20-membered heteroarylthio, 3-20-membered heterocyclicthio, C 1-8 -heteroalkyl-fused C 6-20- Aryl-, C 1-8 -heteroalkyl-C 6-20- Aryl-, NH2, -C(O)R 41 、-C(O)OR 42 、-OC(O)R 43 、-S(O)2R 44 、-S(O)2OR 45 、-OS(O)2R 46 、-P(O)(OR 47 )(OR 48 );

[0400] v represents 0, 1, 2, 3, 4 or 5;

[0401] L represents a chemical bond, C 2-20 alkynyl or Cy; wherein, L can be linked to X1 or R at any position c connected;

[0402] Cy represents a chemical bond, 3-20-membered heterocyclic group, C 6-20 aryl, 5-20-membered heteroaryl, wherein the 3-20-membered heterocyclic group, C 6-20 aryl, 5-20-membered heteroaryl can be optionally fused with a 4-7-membered cycloalkyl group, provided that when the heterocyclic group contains an N atom, the heterocyclic group can be bonded to the carbon atom at the 2-position of the pyrimidine ring in Formula IX through its N atom or C atom;

[0403] R a represents H or -X-R3;

[0404] X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0405] R3 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 、unsubstituted or optionally substituted by 1, 2 or more R d4 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 、-C(O)OR 62 、-OC(O)R 63 、NH2;

[0406] R b represents H or -Y-R4;

[0407] Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-;

[0408] R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted with 1, 2 or more R d5 Substituted with the following groups: C 1-20 Alkyl, -C(O)R 61 、-C(O)OR 62 、-OC(O)R 63 , NH2;

[0409] The condition is R a 、R b Not at the same time H;

[0410] Or, R a 、R b Together with the atoms to which it is attached, it forms an unsubstituted or optionally substituted group consisting of 1, 2 or more R d6 Substituted with the following groups: C 5-20 Cycloalkenyl, 3-20 membered heterocyclyl, 5-20 membered heteroaryl, 6-20 membered aryl;

[0411] Every R d2 、R d4 、R d5 、R d6 the same or different, independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), SO, SO2, unsubstituted or optionally substituted by 1, 2 or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclyloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclicthio, NH2, -C(O)R 31 , -CH2-C(O)R 31 , -C(O)OR 32 , -CH2C(O)OR 32 , -C(O)NHR 32 , -CH2C(O)NHR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 );

[0412] Or, when there are two or more substituents selected from R d2 , R<� d4 , R d5 , R d6 on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R e substituted following groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3- to 20-membered heterocyclic group;

[0413] Each R c is the same or different and independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), an unsubstituted or optionally substituted by 1, 2 or more R e substituted following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl-O-C 6-20 Aryl-, 5-20 membered heteroaryl-N-C 6-20 Aryl-, 5-20 membered heteroaryl-S-C 6-20 Aryl-, 5-20 membered heteroaryl-CH2-C 6-20 Aryl-, C 4-10 Cycloalkyl and C 6-20 Aryl-, 4-10 membered heterocycloalkyl and C6-20 Aryl-, 4- to 10-membered heteroalkenyl-fused C 6-20 Aryl-, C 4-10 Cycloalkyl-C 6-20 Aryl-, 4- to 10-membered heteroalkyl-C 6-20 Aryl-, 4- to 10-membered heteroalkenyl-C 6-20 Aryl-, 5- to 20-membered heteroaryl, C 4-10 Cycloalkyl-fused 5- to 20-membered heteroaryl-, 4- to 10-membered heteroalkyl-fused 5- to 20-membered heteroaryl-, 4- to 10-membered heteroalkenyl-fused 5- to 20-membered heteroaryl-, C 4-10 Cycloalkyl-5- to 20-membered heteroaryl-, 4- to 10-membered heteroalkyl-5- to 20-membered heteroaryl-, 4- to 10-membered heteroalkenyl-5- to 20-membered heteroaryl-, 3- to 20-membered heterocyclic group, C 1-20 Alkoxy, C 2-20 Alkenyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5- to 20-membered heteroaryloxy, 3- to 20-membered heterocyclic oxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5- to 20-membered heteroarylthio, 3- to 20-membered heterocyclic thio, NH2, -C(O)R 31 , -C(O)OR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 );

[0414] For example, the 4- to 10-membered heteroalkyl or 4- to 10-membered heteroalkenyl can be: 1-methylpyrrolidinyl, 1-ethylpyrrolidinyl, 1-cyclopropylpyrrolidinyl, 1-cyclopropylmethylpyrrolidinyl, 5-methyl-4,5-dihydropyridazin-3(2H)-one group, 1-methylazetidinyl, 1-methylpiperidinyl;

[0415] m is an integer from 1 to 10;

[0416] Each R eSame or different, and independently selected from H, halogen, OH, CN, NO2, NH2, oxo(=O), thioxo(=S), O-CONH2, O-CONHR f , unsubstituted or optionally substituted by 1, 2 or more R f substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 , -C(O)OR 42 , -OC(O)R 43 , -S(O)2R 44 , -S(O)2OR 45 , -OS(O)2R 46 , -P(O)(OR 47 )(OR 48 );

[0417] Alternatively, when there are more than two substituents selected from R e on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f substituted with the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclyl;

[0418] Every R f the same or different, independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), unsubstituted or optionally substituted with 1, 2 or more R g Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclyloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclylthio, NH2, -C(O)R 51 、-C(O)OR 52 、-OC(O)R 53 、-S(O)2R 54 、-S(O)2OR 55 、-OS(O)2R 56 、-P(O)(OR 57 )(OR 58 );

[0419] Alternatively, when there are two or more selected from R f When the substituents are substituted, the two substituents may be taken together with the atoms to which they are attached to form an unsubstituted or optionally substituted group with 1, 2 or more R g Substituted with the following groups: C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclyl;

[0420] Each R g is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2;

[0421] Each R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2;

[0422] The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spiro ring), or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, for example, 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the state of nitrogen oxide, -S(O)- or -S(O)2-;

[0423] The C 6-20 Aryl represents a monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a monoaromatic ring or a polyaromatic ring fused together;

[0424] The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic aromatic ring system, the aromatic ring system having 5 to 20 ring atoms and containing 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S.

[0425] According to an embodiment of the present disclosure, L represents an alkynyl group; a mono- or polycyclic C 6-20- aryl group or a mono- or polycyclic C 6-20 -aryl-fused 4- to 7-membered cycloalkyl group, which can be independently optionally substituted at the ortho, para or meta position by one, two or three groups independently selected from fluorine, chlorine, bromine, hydroxyl group, CN, NH2, or by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 10-membered heterocyclic group-C 6-20- aryl, 3- to 10-membered heterocycle, C 1-6 -alkyl, C1-3 -fluoroalkyl, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3- to 10-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 is substituted by the substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 in it, or,

[0426] L represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1, CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-10 membered heterocyclic-C 6-20- aryl, 3-10 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, each of which may optionally be further substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 1.3 ;

[0427] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0428] Heteroaryl is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; In some embodiments, L is selected from 5-membered monocyclic heteroaryl, 5-membered heteroaryl acenaphthene ring, 5-membered heteroaryl and 5-10 membered heteroaryl, 5-membered heteroaryl and 4-7 membered cycloalkyl, 5-membered heteroaryl and 4-7 membered heterocycloalkyl, 6-membered heteroaryl acenaphthene ring, 6-membered heteroaryl and 5-10 membered heteroaryl, 6-membered heteroaryl and 6-membered heteroaryl, 6-membered heteroaryl and 4-7 membered cycloalkyl, 6-membered heteroaryl and 4-7 membered heterocycloalkyl;

[0429] Cycloalkyl may be saturated or partially saturated;

[0430] R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, C 3-11- mono - or bi - heterocyclic, - C 3-10 - cycloalkyl, C 6-20- aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6 - alkyl, 3 - 10 - membered heterocyclic - C 1-6 - alkyl, C 3-10 - cycloalkyl - C 1-6 - alkyl, mono - or bicyclic C 6-20- aryl, 5 - 20 - membered heteroaryl and heterocyclic, which may optionally be selected from OH, O-(C 1-3 - alkyl), halogen, C 1-10- alkyl and C 6-20- aryl;

[0431] R 1.2 and R 1.3 each independently represent H or a group selected from C 1-6- alkyl, mono - or bicyclic C 3-10- cycloalkyl, C 6-20- aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6 alkylene, mono - or bicyclic C 6-20- aryl, 3 - 10 - membered heterocyclic, heteroaromatic ring, CO - NH2, CO - NH - CH3, - CO - N(CH3)2, SO2-(C 1-3 - alkyl), CO - R 1.1 and COOR 1.1 and the groups thereof may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 - alkyl, C 6-20- aryl and COOR 1.1 substituted.

[0432] According to an embodiment of the present disclosure, examples of L may be selected from the following groups:

[0433]

[0434] According to an embodiment of the present disclosure, each R d2 is the same or different and each independently represents hydrogen, halogen, cyano, hydroxy, CF3, C 1-6 - alkyl, C 1-3 - fluoroalkyl, CHF2, CH2F, SO2 - CH3, SO2 - CH2CH3, SO2 - NR 1.2 R 1.3 , C 1-3 - alkyl - CN, C 1-3 - alkyl - OH, C 1-3 - alkyl - OR 1.1 , C1-3 -alkyl-NH2 or C 1-3 -alkyl-NHR 1.1 substituted by substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 ;

[0435] In an embodiment according to the present disclosure, R e may be selected from OH;

[0436] Each R d6 is the same or different and independently represents H, F, Me, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, a mono- or polycyclic C 6-20- aryl or a mono- or polycyclic C 6-20 -aryl-fused 4-7 membered cycloalkyl, a mono- or polycyclic C6-20-heteroaryl-fused 4-7 membered cycloalkyl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl; or,

[0437] Each R d6 is the same or different and independently represents H, F, Me, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3-alkyl - NH2, C 1-3 -alkyl - NHR 1.1 , C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl - C 1-6 -alkyl, C 5-10 -heteroaryl - C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case optionally be substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O - C 1-6- alkyl.

[0438] Alternatively, two and R d6 together with the atoms to which it is attached form a 3 - 11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged cycloalkyl, or a 3 - 11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, the heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl - OR 2.1 , SR 2.1 , C 1-3 -alkyl - SR 2.1 , SO - R 2.1 , C 1-3 -alkyl - SOR 2.1 , SO2 - R 2.1 , C 1-3 -alkyl - SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO - NR 2.1 CH2CO - NR 2.1 , CH2CH2CO - NR 2.1 , CH=CHCO - NR 2.1 , COR 2.1 , CH2COR2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-10 membered heterocyclic-C 6-20- aryl, 3-10 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ;

[0439] R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-10 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, monocyclic or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with substituents selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl; [[ID=,69]]

[0440] R 2.2 and R 2.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, monocyclic or bicyclic C 6-20- aryl, 3-10 membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR2.1 group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- -aryl and COOR 2.1 .

[0441] Each R c is the same or different and independently of one another represents hydrogen, a mono- or polycyclic C 6-20 -aryl or a mono- or polycyclic C 6-20 -aryl and 4-7 membered cycloalkyl, such as C 4-10 cycloalkyl and C 6-20 -aryl-, 4-10 membered heterocycloalkyl and C 6-20 -aryl-, 4-10 membered heterocycloalkenyl and C 6-20 -aryl-, C 4-10 cycloalkyl-C 6-20 -aryl-, 4-10 membered heterocycloalkyl-C 6-20 -aryl-, 4-10 membered heterocycloalkenyl-C 6-20 -aryl-, 5-20 membered heteroaryl, C 4-10 cycloalkyl and 5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl and 5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl and 5-20 membered heteroaryl-, C 4-10 cycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryl-, or selected from 5-20 membered heteroaryl-O-C 6-20 -aryl-, 5-20 membered heteroaryl-N-C 6-20 -aryl-, 5-20 membered heteroaryl-S-C 6-20 -aryl-, 5-20 membered heteroaryl-CH2-C 6-20 -aryl-, the above groups may each independently optionally be substituted in the ortho, para or meta positions by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, CN, NO2, NH2, or by one, two or more substituents selected from OR 4.1 , COOR 4.1 CH2COOR 4.1 , CH2CH2COOR 4.1 , CH=CHCOOR 4.1 , CO-NR 4.1 CH2CO-NR 4.1 , CH2CH2CO-NR 4.1 , CH=CHCO-NR 4.1 , NR 4.2 R 4.3 , CH2-NR 4.2 R 4.3,CH2CH2-NR 4.2 R 4.3 ,C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 4.1 、C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 4.1 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic C 6-20- aryl), 3-10 membered heterocyclyl-C 6-20- Aryl, 3-10 membered heterocyclic ring, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- Aryl-C 1-6 -alkyl, 3-10 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, C 6-20- Aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 4.2 R 4.3 Substituents substituted;

[0442] Or, each R c are identical or different and independently represent a group selected from heterocycle and heteroaryl, which may be optionally substituted in the ortho, para or meta position by one, two or three halogen, OH, oxo, CF3, CHF2 and CH2F groups, or by one, two or more groups selected from OR 4.1 、C 1-3 -alkyl-OR 4.1 SR 4.1 、C 1-3 -alkyl-SR 4.1 ,SO-R 4.1 ,C 1-3 -alkyl-SOR 4.1 ,SO2-R 4.1 ,C 1-3 -alkyl-SO2R 4.1 ,COOR 4.1 ,CH2COOR 4.1 ,CH2CH2COOR 4.1 ,CH=CHCOOR 4.1 ,CO-NR 4.1 CH2CO-NR 4.1 ,CH2CH2CO-NR 4.1 ,CH=CHCO-NR4.1 , COR 4.1 , CH2COR 4.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-10 membered heterocyclic-C 6-20- aryl, 3-10 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 4.1 and NR 4.2 R 4.3 is substituted with substituents of, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 4.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 4.2 R 4.3 ;

[0443] Heterocycle represents a 3-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O;

[0444] Heteroaryl ring is a 5-10 membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; In some embodiments, R4 is selected from a 5-membered monocyclic heteroaryl, a 5-membered heteroarylacenaphthene ring, a 5-membered heteroaryl-fused 5-10 membered heteroaryl, a 5-membered heteroaryl-fused 4-7 membered cycloalkyl, a 5-membered heteroaryl-fused 4-7 membered heterocycloalkyl, a 6-membered heteroarylacenaphthene ring, a 6-membered heteroaryl-fused 5-10 membered heteroaryl, a 6-membered heteroaryl-fused 6-membered heteroaryl, a 6-membered heteroaryl-fused 4-7 membered cycloalkyl, a 6-membered heteroaryl-fused 4-7 membered heterocycloalkyl;

[0445] Cycloalkyl may be saturated or partially saturated;

[0446] R 4.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6-alkyl, 3- to 10-membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5- to 20-membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 5-10 aryl substituents;

[0447] R 4.2 and R 4.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3- to 10-membered heterocycle, heteroaromatic ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 4.1 and COOR 4.1 and the groups of which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 4.1 .

[0448] For example, the 4- to 10-membered heterocyclic group or 4- to 10-membered heterocyclic alkenyl group may be: 1-methylpyrrolidinyl, 1-ethylpyrrolidinyl, 1-cyclopropylpyrrolidinyl, 1-cyclopropylmethylpyrrolidinyl, 5-methyl-4,5-dihydropyridazin-3(2H)-one group, 1-methylazetidinyl, 1-methylpiperidinyl.

[0449] Alternatively, for the compound represented by formula H or formula G according to the present disclosure (for example, one of the compounds represented by formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound, when present, R1 represents hydrogen, a mono- or polycyclic C 6-20 aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two, or three fluorine, chlorine, bromine, iodine, hydroxyl, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3 -CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-N R 1.2 R 1.3、-NR 1.1 CN, -CHO, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 ,COOR 1.1 CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,NR 1.2 R 1.3 ,CH2-NR 1.2 R 1.3 ,CH2CH2-NR 1.2 R 1.3 ,C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclyl-C 6-20- Aryl, 3-20 membered heterocyclic ring, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- Aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- Alkyl, C 6-20- Aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by a substituent, each of which may be optionally substituted by 1, 2 or more substituents selected from OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3- Alkyl-NHOH, -C 1-3- Alkyl-CO-NHOH, -CO-NHOH, -C 1-3 -alkyl-NH-CO-NR 1.2 R 1.3 、-NR 1.1 CN, -CHO, C 2-6 -alkenyl, -OC 3-8 -cycloalkyl, COOR 1.1 、C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 、C 1-3 -alkyl-CONHR1.1 , -OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- -aryl and NR 1.2 R 1.3 substituted by the substituents in; wherein, R 1.1 , R 1.2 , R 1.3 has the definitions described in the context herein.

[0450] Alternatively, for a compound represented by Formula H or Formula G according to the present disclosure (such as one of the compounds represented by Formulas I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound, when present, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three halogens, OH, CN, NH2, -NHOH, -C 1-3 -alkyl-NHOH, -C 1-3 -alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, nitro, oxo, CF3, CHF2 and CH2F, or substituted by one, two or more groups selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10-cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20 aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 is substituted by substituents of, each of which may optionally be further substituted by OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3 -alkyl-NHOH, -C 1-3- alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 by one, two or more substituents selected from; wherein, R 1.1 , R 1.2 , R 1.3 has the definitions as described in the context herein.

[0451] Alternatively, for a compound of formula H or formula G according to the present disclosure (e.g., one of the compounds of formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or prodrug compound thereof, when present, R2 represents hydrogen, a single- or polycyclic C 6-20 aryl, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by one, two or more substituents selected from OR2.1 , COOR 2.1 , CH2COOR 2.1 , C(CH3)2COOR 2.1 , CF2COOR 2.1 , CHFCOOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 , CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 , - cycloalkyl, COOR 2.1 , - C 3-8- , cycloalkyl, CO-NR 2.1 , - C 3-8- , cycloalkyl, C 1-3 , - alkyl - (monocyclic or polycyclic - C 6-20 , aryl), 3 - 20 - membered heterocyclic group - C 6-20 , aryl, 3 - 20 - membered heterocycle, C 1-6 , - alkyl, C 1-3 , - fluoroalkyl, CF3, CHF2, CH2F, C 6-20 , aryl - C 1-6 , - alkyl, 3 - 20 - membered heterocyclic - C 1-6 , - alkyl, 5 - 20 - membered heteroaryl - C 1-6- , alkyl, C 6-10 , - aryl, C 1-3 , - alkyl - SOR 2.1 , C 1-3 , - alkyl - SO2R 2.1 , SO2 - CH3, SO2 - CH2CH3 and SO2 - NR 2.2 R 2.3 , are substituted by substituents of 2.3 , and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, CN, C 1-3 , - alkyl - CN, - SH, - NH2, - NHOH, - C 1-3- , alkyl - NHOH, - C 1-3- , alkyl - CO - NHOH, - CO - NHOH, - C 1-3 , - alkyl - NH - CO - NR 1.2 R 1.3 , - NR1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 2.2 R 2.3 substituted by the substituents in, CCOOR 2.1 ; wherein, R 2.1 , R 2.2 , R 2.3 has the definitions described in the context herein.

[0452] Alternatively, a compound represented by Formula H or Formula G according to the present disclosure (e.g., one of the compounds represented by Formulas I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound, when present, R2 represents a group selected from heterocycle and heteroaryl, which may optionally be independently optionally substituted at the ortho, para or meta position by one, two or three halogen, OH, CN, NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO - NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, nitro, oxo, CF3, CHF2 and CH2F, or substituted by one, two or more groups selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , COOR 2.1 -C3-8 -cycloalkyl, CO-NR 2.1 -C 3-8 -cycloalkyl, CH2CH2COOR 2.1 ,CH=CHCOOR 2.1 ,CO-NR 2.1 CH2CO-NR 2.1 ,CH2CH2CO-NR 2.1 ,CH=CHCO-NR 2.1 ,COR 2.1 ,CH2COR 2.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 aryl, C 1-6 -alkyl, C 6-20 -aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3- to 20-membered heterocyclic-C 6-20 aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 is substituted with substituents of, each of which may optionally be further substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 ; wherein, R 2.1 , R 2.2 , R 2.3 has the definitions described in the context hereof.

[0453] Alternatively, for a compound represented by Formula H or Formula G according to the present disclosure (such as one of the compounds represented by Formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or prodrug compound thereof, when present, R2 and R 2’ together with the atom to which it is attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused combination or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, and the heterocycle is unsubstituted or optionally substituted at the ortho, para or meta positions with 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1, C 1-3 -alkyl-OR 2.1 , C 1-3 -alkyl-O-C 1-3 -alkyl-COOH, C 1-3 -alkyl-O-C 1-3 -alkyl-CONR 2.1 , C 1-3 -alkyl-phosphoric acid, C 1-3 -alkyl-O-C(O)-OR 2.1 , C 1-3 -alkyl-O-C(O)-NR 2.1 , C 1-3 -alkyl-O-C(=O)-C 1-3 -alkyl-(O-C 1-3 -alkyl)v, C 1-3 -alkyl-O-C(=O)-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-O-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-N-C 1-6 -alkyl-COOR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR[[ID=]5] 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 , CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6-alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 、NR 2.2 R 2.3 、C 6-20- aryl and NR 2.2 R 2.3 ; each said substituent may in turn be optionally substituted by one, two or more substituents selected from OH, CN, C 1-3 -alkyl-CN, C 1-3 -alkyl-NH2, -SH, -NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 、-NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 、C 1-3 -alkyl-COOR 1.1 、CONHR 1.1 、C 1-3 -alkyl-CONHR 1.1 、-OR 1.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 wherein, R 2.1 、R 1.2 、R 1.3 、v have the definitions as described in the context of this specification.

[0454] Alternatively, a compound represented by formula H or formula G according to the present disclosure (for example, one of the compounds represented by formulas I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound, when present, each R 31 、R 32 、R 33 、R 34 、R35 , R 36 , R 37 , R 38 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 are the same or different and are each independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2; each of the above groups may optionally be substituted by OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO - NHOH, -CO - NHOH, -C 1-3- alkyl-NH - CO - NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 by one, two or more substituents selected from; wherein, R 1.1、R 1.2 、R 2.1 、R 2.3 has the meaning given in the context of this document.

[0455] Alternatively, according to the compound represented by Formula H or Formula G of the present disclosure (e.g., one of the compounds represented by Formulas I to IX), its racemate, stereoisomer, tautomer, isotope-labeled substance, solvate, polymorph, pharmaceutically acceptable salt or prodrug compound, when present, each R c the same or different, independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), unsubstituted or optionally substituted with 1, 2 or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, C 6-20 Aryl, C 1-6 Alkyl-C 4-10 Heterocycloalkyl, C 1-6 Alkyl-C 4-10 Heterocycloalkenyl, C 1-6 Alkyl-C 6-20 Aryl, C 1-6 Alkyl-C 5-20 Heteroaryl, 5-20 membered heteroaryl-OC 6-20 Aryl-, 5-20 membered heteroaryl-NC 6-20 Aryl-, 5-20 membered heteroaryl-SC 6-20 Aryl-, 5-20 membered heteroaryl-CH2-C 6-20 Aryl-, C 4-10 Cycloalkyl C 6-20 Aryl-, 4-10 membered heterocycloalkyl and C 6-20 Aryl-, 4-10 membered heterocycloalkenyl and C 6-20 Aryl-, C 4-10 Cycloalkyl-C 6-20 Aryl-, 4-10 membered heterocycloalkyl-C 6-20 Aryl-, 4-10 membered heterocycloalkenyl-C 6-20 Aryl-, 5-20 membered heteroaryl, C 4-10 Cycloalkyl and 5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl and 5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl and 5-20 membered heteroaryl-, C 4-10 Cycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryl-, 3-20 membered heterocyclyl, C1-20 Alkyloxy, C 2-20 Vinyloxy, C 2-20 Alkynyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, C 3-20 Cycloalkynyloxy, C 6-20 Aryloxy, 5 - 20 - membered heteroaryloxy, 3 - 20 - membered heterocycloxy, C 1-20 Alkylthio, C 2-20 Vinylthio, C 2-20 Alkynylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, C 3-20 Cycloalkynylthio, C 6-20 Arylthio, 5 - 20 - membered heteroarylthio, 3 - 20 - membered heterocyclthio, NH2, -C(O)R 31 , -C(O)OR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 ); wherein, R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 has the definitions described in the context herein.

[0456] Unless otherwise defined, in the compounds described in any one of Formulas I to IX in the context of the present disclosure, when some substituents are defined as two connected groups (such as in the form of "group 1 - group 2", where group 1 and group 2 are the same or different), the position at which the substituent forms a bond in the compounds described in any one of Formulas I to IX is not particularly limited. For example, it can be that group 1 is bonded to the connection position in the compounds described in any one of Formulas I to IX, or it can also be that group 2 is bonded to the connection position in the compounds described in any one of Formulas I to IX, as long as the above - mentioned bonding conforms to the valence bond theory. And, the connection position between the two connected groups (such as group 1 and group 2) is not particularly limited, as long as the above - mentioned connection conforms to the valence bond theory.

[0457] For the purpose of exemplary illustration, for example, C 6-20- aryl - C 1-6 - alkyl, 5 - 20 - membered heteroaryl - C 1-6 alkyl, C1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 、3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl and other groups, which may represent C 6-20- aryl-C 1-6 -alkyl-, 5-20 membered heteroaryl-C 1-6 alkyl-, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl)-, 3-20 membered heterocyclic-C 6-20- aryl-, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 -, 3-20 membered heterocyclic-C 1-6 -alkyl-, C 3-10 -cycloalkyl-C 1-6 -alkyl-, may also represent -C 6-20- aryl-C 1-6 -alkyl, -5-20 membered heteroaryl-C 1-6 alkyl, -C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), -3-20 membered heterocyclic-C 6-20- aryl, -5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 、-3-20 membered heterocyclic-C 1-6 -alkyl, -C 3-10 -cycloalkyl-C 1-6 -alkyl.

[0458] It should be understood that when for the above "group 1 - group 2" form, if a chemical bond "-" is added to the left of group 1 or to the right of group 2, it means that the connection position in the compound described in any one of formulas I to IX has been determined, and the position where it forms a bond in the compound described in any one of formulas I to IX is the corresponding group to which the chemical bond is added.

[0459] The present disclosure also provides a method for preparing the compound shown in formula H, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the preparation method includes reacting a compound of formula A1 with a compound of formula B1 to obtain a compound of formula G:

[0460]

[0461] Wherein, LG is a leaving group, such as Cl, Br or I;

[0462] X1, L, W, R a , R b , R c , R2, R 2’ , m independently of one another have the definitions described above.

[0463] The present disclosure also provides a method for preparing a compound represented by formula G, a racemate, a stereoisomer, a tautomer, an isotope-labeled compound, a solvate, a polymorph, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein the preparation method includes reacting a compound of formula A with a compound of formula B to obtain a compound of formula G:

[0464]

[0465] And optionally, derivatizing the compound of formula G into its stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug;

[0466] Wherein, LG is a leaving group, such as Cl, Br or I;

[0467] Cy, W, R a , R b , R c , R2, R 2’ , m independently of one another have the definitions described above.

[0468] According to an embodiment of the present disclosure, if necessary, the reaction can be carried out in the presence of a protecting group on the compound of formula A1, A2, B1 or B2. For example, the protecting group can be selected from amino protecting groups, hydroxyl protecting groups, etc. Suitable protecting groups can be selected from C 1-40 alkyl, C 6-20 arylC 1-40 alkyl-, such as tert-butyl, isopropyl, benzyl, tert-butoxycarbonyl (Boc), 2-biphenyl-2-propoxycarbonyl, benzyloxycarbonyl, fluorenylmethoxycarbonyl (Fmoc), trifluoroacetyl.

[0469] According to an embodiment of the present disclosure, the preparation method can be carried out in the presence of a solvent such as an organic solvent. For example, the organic solvent can be selected from at least one of the following: alcohols such as methanol, ethanol, isopropanol, and n-butanol; ethers such as ethyl propyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dimethyl ethylene glycol, diphenyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, isopropyl ethyl ether, methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, dichloroethyl ether, and polyethers of ethylene oxide and / or propylene oxide; aliphatic, cycloaliphatic or aromatic hydrocarbons such as pentane, hexane, heptane, octane, nonane, and those that may be substituted by fluorine and chlorine atoms such as methylene chloride, dichloromethane, chloroform, carbon tetrachloride, fluorobenzene, chlorobenzene or dichlorobenzene; cyclohexane, methylcyclohexane, petroleum ether, octane, benzene, toluene, chlorobenzene, bromobenzene, xylene; esters such as methyl acetate, ethyl acetate, butyl acetate, isobutyl acetate and dimethyl carbonate, dibutyl carbonate or ethylene carbonate.

[0470] The present disclosure also provides a pharmaceutical composition comprising at least one of a therapeutically effective amount of a compound represented by formula H or formula G (for example, any one of the compounds represented by formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound.

[0471] According to an embodiment of the present disclosure, the pharmaceutical composition further includes one or more pharmaceutically acceptable excipients.

[0472] According to an embodiment of the present disclosure, the pharmaceutical composition may further contain one or more additional therapeutic agents. The additional therapeutic agents can be selected from therapeutic agents having the same or different targets as the compounds of the present disclosure, such as cancer therapeutic agents.

[0473] The present disclosure also provides the use of at least one of a compound represented by formula H or formula G (for example, one of the compounds represented by formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound in the preparation of a drug.

[0474] The drug can be used for preventing or treating diseases.

[0475] The present invention also provides a method for preventing or treating a disease, comprising administering to a patient in need at least one of a compound represented by formula H or formula G (for example, one of the compounds represented by formula I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound.

[0476] According to an embodiment of the present invention, the disease may be a PDE4B-mediated disease, or a disease mediated at least by PDE4.

[0477] For example, the disease mediated at least by PDE4 is selected from diseases mediated by PDE4, or diseases mediated by at least one (such as 1, 2, 3, or 4) of PDE1, PDE2, PDE3, and PDE5.

[0478] For example, the drug may be used for preventing or treating diseases mediated by PDE4 and at least one (such as 1, 2, 3, or 4) of PDE1, PDE2, PDE3, and PDE5.

[0479] According to an embodiment of the present disclosure, the PDE4 is selected from PDE4A, PDE4B (such as PDE4B2), PDE4C, and PDE4D (such as PDE4D2).

[0480] According to an embodiment of the present disclosure, the PDE1 is selected from PDE1A, PDE1B, and PDE1C.

[0481] According to an embodiment of the present disclosure, the PDE2 is selected from PDE2A.

[0482] According to an embodiment of the present disclosure, the PDE3 is selected from PDE3A and PDE3B.

[0483] According to an embodiment of the present disclosure, the PDE5 is selected from PDE5A.

[0484] According to an embodiment of the present invention, the diseases include, but are not limited to, respiratory inflammatory diseases, inflammatory bowel diseases, arthritic diseases, skin inflammatory diseases, eye inflammatory diseases, diseases of the peripheral or central nervous system, degenerative lesions of the central nervous system, Alzheimer's Disease (AD), Non-alcoholic Steatohepatitis (NASH), Idiopathic Pulmonary Fibrosis (IPF) or pulmonary hypertension associated therewith, chronic obstructive pulmonary disease (COPD) or pulmonary hypertension associated therewith, hepatic fibrosis (HF), renal fibrosis, benign prostatic hyperplasia (BPH), gastroesophageal reflux disease, obstructive sleep apnea, and coronary artery disease or cancer.

[0485] According to an embodiment of the present invention, the cancer includes, but is not limited to, one selected from the following: gastric cancer, bladder cancer, blood cancer, bone cancer, brain cancer, breast cancer, central nervous system cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, gallbladder cancer, gastrointestinal cancer, genital cancer, genitourinary cancer, head cancer, kidney cancer, laryngeal cancer, liver cancer, lung cancer, muscle tissue cancer, cervical cancer, oral or nasal mucosa cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, spleen cancer, small intestine cancer, colorectal cancer, testicular cancer, and / or thyroid cancer.

[0486] According to an embodiment of the present invention, since the compounds of the present disclosure have specific tissue distribution and / or low hERG inhibitory effect, the diseases are preferably selected from those diseases that are particularly advantageous when prevented or treated with compounds having specific tissue distribution and / or low hERG inhibitory effect.

[0487] For example, the lesions (i.e., the diseased parts) of the diseases include the respiratory system, digestive system, excretory system, and / or reproductive system, such as the liver, kidney, and / or prostate. For this purpose, the drug can be a targeted drug for the respiratory system, digestive system, excretory system, and / or reproductive system, such as a liver-targeted drug, a kidney-targeted drug, and / or a prostate-targeted drug.

[0488] When used as a medicine, the compounds of the present disclosure can be administered in the form of a pharmaceutical composition. These compositions can be prepared in a manner well-known in the pharmaceutical art and can be administered by a variety of routes, depending on whether local or systemic treatment is required and the area being treated. They can be administered locally (e.g., transdermally, dermally, ophthalmically and mucosally including intranasally, vaginally and rectally), by the lungs (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheally, intranasally), orally or parenterally. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranially such as intrathecally or intraventricularly. Parenteral administration can be in the form of a single large dose, or can be administered, for example, by means of a continuous perfusion pump. Medicinal compositions and formulations for local administration can include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, water, powder or oily bases, thickening agents, etc. may be necessary or desirable.

[0489] In preparing the compositions of the present disclosure, the active ingredient is generally admixed with an excipient, diluted by the excipient or enclosed within a carrier such as in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it can be a solid, semi-solid or liquid substance and serves as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or dissolved in a liquid vehicle); ointments, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders containing, for example, up to 10% by weight of the active compound.

[0490] Some examples of suitable excipients include lactose, glucose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methylcellulose. The formulations can also contain: lubricants such as talc, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; preservatives such as methyl benzoate and propyl hydroxybenzoate; sweetening and flavoring agents. The compositions of the present disclosure can be formulated by using methods known in the art so as to provide a rapid-release, sustained-release or delayed-release action of the active ingredient after administration to a patient.

[0491] The compositions can be formulated in unit dosage forms, each dosage containing about 5 - 1000 mg, more usually about 100 - 500 mg of the active ingredient. The term "unit dosage form" refers to physically discrete units suitable as a single dosage for human patients and other mammals, each unit containing a predetermined quantity of the active substance calculated to produce the desired therapeutic effect in admixture with a suitable pharmaceutical excipient.

[0492] The effective dosage range of the active compounds can be very wide and is usually administered in a pharmaceutically effective amount. However, it is understood that the amount of the compound actually administered is usually determined by the physician according to relevant circumstances, which include the disorder to be treated, the route of administration selected, the actual compound to be administered; the age, weight and response of the individual patient; the severity of the patient's symptoms, etc.

[0493] For the preparation of solid compositions such as tablets, the main active ingredient is mixed with a pharmaceutical excipient to form a solid preformulation composition that is a homogeneous mixture containing the compounds of the present disclosure. When these preformulation compositions are said to be homogeneous, it means that the active ingredient is usually uniformly distributed throughout the composition, such that the composition can be easily divided into equally effective unit dosage forms such as tablets, pills and capsules. Then the solid preformulation is divided into unit dosage forms of the above types containing, for example, about 0.1 to 1000 mg of the active ingredient of the present disclosure.

[0494] The tablets or pills of the present disclosure can be coated or compounded to obtain dosage forms that provide the advantage of a long-acting effect. For example, the tablets or pills contain an inner dose and an outer dose component, the latter being in the form of a coating for the former. The two components can be separated by an enteric layer, which is used to prevent disintegration in the stomach so that the inner component passes intact through the duodenum or is released in a delayed manner. A variety of substances can be used for such enteric layers or coating agents, and such substances include a variety of high molecular acids and mixtures of high molecular acids with such substances as shellac, cetyl alcohol and cellulose acetate.

[0495] Liquid forms in which the compounds and compositions of the present disclosure can be incorporated for oral or injectable administration include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions; and emulsions flavored with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil; and elixirs and similar pharmaceutical vehicles.

[0496] Compositions for inhalation or insufflation include solutions and suspensions, powders dissolved in pharmaceutically acceptable aqueous or organic solvents or mixtures thereof. The liquid or solid compositions can contain suitable pharmaceutically acceptable excipients as described above. In certain embodiments, the composition is administered by the oral or nasal respiratory route to achieve local or systemic effects. The composition can be atomized by using an inert gas. The atomized solution can be inhaled directly by an atomizing device, or the atomizing device can be connected to a face mask tent or an intermittent positive pressure ventilator. The solution, suspension or powder composition can be administered orally or nasally by a device that delivers the formulation in a suitable manner.

[0497] The amount of the compound or composition administered to a patient is not fixed and depends on the drug administered, the purpose of administration such as prophylaxis or treatment; the condition of the patient, the mode of administration, etc. In therapeutic applications, a composition in an amount sufficient to cure or at least partially inhibit the disease and the symptoms of its complications may be administered to a patient suffering from the disease. The effective dose should depend on the disease state being treated and the judgment of the attending clinician, which depends on factors such as the severity of the disease, the age, weight and general condition of the patient, etc.

[0498] The composition administered to a patient may be in the form of the above-mentioned pharmaceutical composition. These compositions can be sterilized by conventional sterilization techniques or can be filter-sterilized. The aqueous solutions can be packaged and used as such, or lyophilized, and before administration, the lyophilized preparation is mixed with a sterile aqueous carrier. The pH of the compound preparation is generally 3 to 11, more preferably 5 to 9, and most preferably 7 to 8. It is understood that the use of certain of the foregoing excipients, carriers or stabilizers can result in the formation of drug salts.

[0499] The therapeutic dose of the compounds of the present disclosure can depend on, for example: the specific use for treatment, the mode of administering the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of the compounds of the present disclosure in the pharmaceutical composition is not fixed and depends on various factors, which include the dose, chemical properties (such as hydrophobicity) and the route of administration. For example, the compounds of the present disclosure can be provided in a physiological buffer aqueous solution containing about 0.1 to 10% w / v of the compound for parenteral administration. Some typical dose ranges are about 1 μg / kg to about 1 g / kg body weight per day. In some embodiments, the dose range is about 0.01 mg / kg to about 100 mg / kg body weight per day. The dose is likely to depend on such variables as the type and progression of the disease or disorder, the general health status of the specific patient, the relative biological potency of the selected compound, the excipient formulation and its route of administration. The effective dose can be extrapolated from the dose-response curve derived from in vitro or animal model test systems.

[0500] Beneficial effects

[0501] The present disclosure provides new compounds having a pyrimidine-fused ring as a novel parent nucleus, novel side chains, novel linkers and substituents. The compounds of the present disclosure have excellent PDE4B inhibitory activity, even at the pmol level of inhibitory activity. The compounds of the present disclosure also have selective PDE4B inhibitory activity, especially the selective inhibitory activity of PDE4B / 4D. Some of the compounds unexpectedly also have dual-target or multi-target inhibitory activity.

[0502] The present disclosure can be used to treat respiratory inflammatory diseases, inflammatory bowel diseases, arthritis inflammatory diseases, skin inflammatory diseases, eye inflammatory diseases, and diseases or cancers of the peripheral or central nervous system. Moreover, the compounds of the present disclosure also have specific tissue distribution and / or low hERG inhibition, thus having an expected application prospect of tissue-targeted drugs and improved tissue toxicity.

[0503] Term Definitions and Explanations

[0504] Unless otherwise specified, the definitions of groups and terms recorded in the specification and claims of this application, including their definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific compounds in examples, etc., can be combined and combined with each other arbitrarily. The group definitions and compound structures after such combination and combination should be understood to be within the scope recorded in the specification and / or claims of this application.

[0505] Unless otherwise specified, the numerical ranges recorded in this specification and claims are equivalent to recording at least each specific integer value therein. For example, the numerical range "1-20" is equivalent to recording each integer value in the numerical range "1-10", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and each integer value in the numerical range "11-40", namely 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In addition, when certain numerical ranges are described as "numbers", it should be understood that the two endpoints of the range, each integer within the range, and each decimal within the range are recorded. For example, "numbers from 0 to 10" should be understood to record not only each integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, but also at least the sum of each integer and 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 respectively.

[0506] It should be understood that in the description of 1, 2 or more, "more" should refer to greater than 2, for example, an integer greater than or equal to 3, such as 3, 4, 5, 6, 7, 8, 9 or 10.

[0507] The term "halogen" means fluorine, chlorine, bromine and iodine.

[0508] The term "C 1-20 alkyl" should be understood to mean a straight-chain or branched-chain saturated monovalent hydrocarbon group having 1 to 20 carbon atoms. For example, "C 1-10 alkyl" means straight-chain and branched-chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, "C 1-6"Alkyl" means straight-chain and branched alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. The alkyl groups are, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, etc. or their isomers.

[0509] The term "C 2-20 alkenyl" should be understood to preferably mean a straight-chain or branched monovalent hydrocarbon group containing 1, 2 or more double bonds and having 2 to 20 carbon atoms, preferably "C 2-10 alkenyl". "C 2-10 alkenyl" should be understood to preferably mean a straight-chain or branched monovalent hydrocarbon group containing 1, 2 or more double bonds and having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, for example, having 2, 3, 4, 5 or 6 carbon atoms (i.e., C 2-6 alkenyl), having 2 or 3 carbon atoms (i.e., C 2-3(alkenyl). It is to be understood that in the case where the alkenyl contains more than one double bond, the double bonds may be separated from each other or conjugated. The alkenyl is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1-methylbut-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl.

[0510] The term "C 2-20 alkynyl" is to be understood as denoting a straight-chain or branched monovalent hydrocarbon group that contains 1, 2 or more triple bonds and has 2 to 20 carbon atoms, preferably "C 2-10 alkynyl". The term "C 2-10 alkynyl" is preferably to be understood as denoting a straight-chain or branched monovalent hydrocarbon group that contains 1, 2 or more triple bonds and has 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, for example, having 2, 3, 4, 5 or 6 carbon atoms (i.e., "C 2-6 alkynyl"), having 2 or 3 carbon atoms ("C 2-3"alkynyl"). The alkynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl or 3,3-dimethylbut-1-ynyl. In particular, the alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0511] The term "C 3-20 cycloalkyl" should be understood to represent a saturated or unsaturated (such as partially unsaturated) monovalent monocyclic, bicyclic (such as fused, bridged, spiro) hydrocarbon ring or tricyclic alkane having 3 to 20 carbon atoms, preferably "C 3-10 cycloalkyl". The term "C 3-10 cycloalkyl" should be understood to represent a saturated monovalent monocyclic, bicyclic (such as bridged, spiro) hydrocarbon ring or tricyclic alkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C 3-10 cycloalkyl can be a monocyclic hydrocarbon group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or a bicyclic hydrocarbon group such as borneolyl, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonyl, 2,6-diazaspiro[3,4]octyl, or a tricyclic hydrocarbon group such as adamantyl.

[0512] Those skilled in the art should understand that the term "C 3-20 cycloalkyl" is not aromatic. Moreover, when the above "C 3-20 cycloalkyl" is unsaturated, it can have more than 1 carbon-carbon double bond and / or more than 1 carbon-carbon triple bond. Among them, when "C 3-20When the "cycloalkyl group" has a carbon-carbon double bond, it can also be called "C 3-20 cycloalkenyl group"; when "C 3-20 cycloalkyl group" has a carbon-carbon triple bond, it can also be called "C 3-20 cycloalkynyl group".

[0513] Unless otherwise defined, the term "3- to 20-membered heterocyclic group" refers to a saturated or unsaturated non-aromatic ring or ring system, for example, which is a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spiro ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, for example 1, 2, 3, 4, 5 or more heteroatoms selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the states of nitrogen oxides, -S(O)- or -S(O)2-. Preferably, the heterocyclic group can be selected from "3- to 10-membered heterocyclic groups". The term "3- to 10-membered heterocyclic group" means a saturated or unsaturated non-aromatic ring or ring system and contains at least one heteroatom selected from O, S and N. The heterocyclic group can be connected to the rest of the molecule through any one of the carbon atoms or a nitrogen atom (if present). The heterocyclic group can include fused or bridged rings and spiro rings. In particular, the heterocyclic group can include but is not limited to: a 4-membered ring, such as azetidinyl, oxetanyl; a 5-membered ring, such as tetrahydrofuranyl, dioxolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl; or a 6-membered ring, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or a 7-membered ring, such as diazepanyl. Optionally, the heterocyclic group can be benzo-fused. The heterocyclic group can be bicyclic, for example but not limited to a 5,5-membered ring, such as hexahydrocyclopenta[c]pyrrol-2(1H)-yl ring, or a 5,6-membered bicyclic ring, such as hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl ring. The heterocyclic group can be partially unsaturated, that is, it can contain 1, 2 or more double bonds, for example but not limited to dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrrolyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl, or, it can be benzo-fused, for example but not limited to dihydroisoquinolinyl. When the 3- to 20-membered heterocyclic group is connected to other groups to form the compounds of the present disclosure, it can be the carbon atom on the 3- to 20-membered heterocyclic group connected to other groups, or it can be the heterocyclic atom on the 3- to 20-membered heterocyclic ring connected to other groups. For example, when the 3- to 20-membered heterocyclic group is selected from piperazinyl, it can be the nitrogen atom on piperazinyl connected to other groups. Or when the 3- to 20-membered heterocyclic group is selected from piperidinyl, it can be the nitrogen atom on the piperidine ring and the carbon atom in the para position connected to other groups. For example, the substituted 4- to 10-membered heterocyclic group can be selected from: 1-methylpyrrolidinyl, 1-ethylpyrrolidinyl, 1-cyclopropylpyrrolidinyl, 1-cyclopropylmethylpyrrolidinyl, 5-methyl-4,5-dihydropyridazin-3(2H)-one group, 1-methylazetidinyl, 1-methylpiperidinyl;

[0514] The term "C6-20 "Aryl" should preferably be understood to mean a monocyclic, bicyclic (such as a fused ring, bridged ring, spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms and being monovalent, aromatic or partially aromatic, which may be a monoaromatic ring or a polyaromatic ring fused together, preferably "C 6-14 aryl". The term "C 6-14 aryl" should preferably be understood to mean a monovalent, aromatic or partially aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms ("C 6-14 aryl"), in particular a ring having 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, or a ring having 9 carbon atoms ("C9 aryl"), such as indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl"), such as tetrahydronaphthyl, dihydronaphthyl or naphthyl, or a ring having 13 carbon atoms ("C 13 aryl"), such as fluorenyl, or a ring having 14 carbon atoms ("C 14 aryl"), such as anthracenyl. When the C 6-20 aryl is substituted, it may be mono-substituted or multi-substituted. Moreover, there is no restriction on the substitution site, for example, it may be ortho-substituted, para-substituted or meta-substituted.

[0515] The term "5-20 membered heteroaryl" should be understood to include monocyclic, bicyclic (such as fused, bridged, spiro) or tricyclic aromatic ring systems having 5 to 20 ring atoms and containing 1-5 heteroatoms independently selected from N, O and S, such as "5-14 membered heteroaryl". The term "5-14 membered heteroaryl" should be understood to include monocyclic, bicyclic or tricyclic aromatic ring systems having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms, especially 5 or 6 or 9 or 10 carbon atoms, and containing 1-5, preferably 1-3 heteroatoms independently selected from N, O and S and, additionally, may be benzo-fused in each case. "Heteroaryl" also refers to groups in which the heteroaromatic ring is fused to one, two or more aryl, cycloaliphatic or heterocyclic rings, where the connecting radical or point is on the heteroaromatic ring. Non-limiting examples of the term heteroaryl include, for example, pyridyl, pyrazinyl, furyl, thienyl, pyrimidinyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, 1,2,4-Thiazolyl, pyridazinyl; and 1-, 2-, 3-, 5-, 6-, 7-, or 8-indazolyl, 1-, 3-, 4-, 5-, 6-, or 7-isoindolyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-indazolyl, 2-, 4-, 5-, 6-, 7-, or 8-purinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, or 9-quinolizinyl, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolinyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolinyl, 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl, 2-, 3-, 4-, 5-, or 6-naphthyridinyl, 2-, 3-, 5-, 6-, 7-, or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl, 2-, 4-, 6-, or 7-pteridinyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-4aH-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbazolylcarbazolyl, 1-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-carbolinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9-, or 10-phenanthridinyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-acridinyl, 1-, 2-, 4-, 5-, 6-, 7-, 8-, or 9-pyridinyl, 2-, 3-, 4-, 5-, 6-, 8-, 9-, or 10-phenanthroline, 1-, 2-, 3-, 4-, 6-, 7-, 8-, or 9-phenazine, 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9-, or 10-phenothiazine, 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9-, or 10-phenazine, 2-, 3-, 4-, 5-, 6-, or 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-benzoisoquinolinyl, 2-, 3-, 4-, or thiopheno[2,3-b]furanyl, 2-, 3-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-7H-pyrazino[2,3-c]carbazolyl, 2-, 3-, 5-, 6-, or 7-2H-furo[3,2-b]-pyranyl, 2-, 3-, 4-, 5-, 7-, or 8-5H-pyrido[2,3-d]-phthalazinyl, 1-, 3-, or 5-1H-pyrazolo[4,3-d]-thiazolyl, 2-, 4-, or 5-1H-imidazo[4,5-d]thiazolyl, 3-, 5-, or 8-pyrazino[2,3-d]pyridazinyl, 2-, 3-, 5-, or 6-imidazo[2,1-b]thiazolyl, 1-, 3-, 6-, 7-, 8-, or 9-furo[3,4-c]cinnolinyl, 1-, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10, or 11-4H-pyrido[2,3-c]carbazolyl, 2-, 3-, 6-, or 7-imidazo[1,2-b][1,2,4] Triazinyl, 7-benzo[b]thienyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 2-, 4-, 5-, 6- or 7-benzimidazolyl, 2-, 4-, 4-, 5-, 6- or 7-benzothiazolyl, 1-, 2-, 4-, 5-, 6-, 7-, 8- or 9-benzoxapinyl, 2-, 4-, 5-, 6-, 7- or 8-benzazinyl, 1-, 2-, 3-, 5-, 6-, 7-, 8-, 9-, 10- or 11-1H-pyrrolo[1,2-b][2]benzazapinyl. Typical fused heteroaryl groups include, but are not limited to, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 2-, 3-, 4-, 5-, 6- or 7-benzo[b]thienyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 2-, 4-, 5-, 6- or 7-benzimidazolyl and 2-, 4-, 5-, 6- or 7-benzothiazolyl. When the 5- to 20-membered heteroaryl group is linked to other groups to form the compounds of the present disclosure, it can be the carbon atoms on the 5- to 20-membered heteroaryl ring that are linked to other groups, or the heteroatoms on the 5- to 20-membered heteroaryl ring that are linked to other groups. When the 5- to 20-membered heteroaryl group is substituted, it can be mono-substituted or multi-substituted. And there is no limitation on its substitution site. For example, the hydrogen atom linked to a carbon atom on the heteroaryl ring can be substituted, or the hydrogen atom linked to a heteroatom on the heteroaryl ring can be substituted.,

[0516] The term "spirocycle" refers to a ring system in which two rings share one ring-forming atom.

[0517] The term "fused ring" refers to a ring system in which two rings share two ring-forming atoms.

[0518] The term "bridged ring" refers to a ring system in which two rings share more than three ring-forming atoms.

[0519] Unless otherwise specified, heterocyclic group, 5- to 20-membered heteroaryl group or heteroarylene group include all their possible isomeric forms, such as their position isomers. Therefore, for some illustrative and non-limiting examples, it can include forms substituted or bonded to other groups at one, two or more positions among their 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12- positions, etc. (if any), including pyridin-2-yl, pyridin-2-ylidene, pyridin-3-yl, pyridin-3-ylidene, pyridin-4-yl and pyridin-4-ylidene; thienyl or thienylene group includes thien-2-yl, thien-2-ylidene, thien-3-yl and thien-3-ylidene; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl.

[0520] The term "oxo (=O)" means that the hydrogen on a non-oxygen atom is replaced or a lone pair of electrons is replaced by oxygen. For example, after being oxo-substituted, it becomes after being oxo-substituted, it becomes

[0521] Unless otherwise specified, the definitions of the terms herein also apply to groups containing such terms. For example, C 1-6 the definition of alkyl also applies to C 1-6 alkyloxy, C 3-8 cycloalkyl-C 1-6 alkyl-, etc.

[0522] In the context of the present disclosure, "-", "--", "---" or on a substituent are all intended to mark the chemical bond for the substituent to connect;

[0523] Those skilled in the art can understand that the compounds shown in Formula I can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; if these compounds contain both an acidic center (such as a carboxyl group) and a basic center (such as an amino group), they can also form inner salts.

[0524] The compounds of the present disclosure can exist in the form of solvates (such as hydrates), where the compounds of the present disclosure contain a polar solvent, especially water, methanol or ethanol, as a structural element of the crystal lattice of the compound. The amount of the polar solvent, especially water, can exist in a stoichiometric ratio or a non-stoichiometric ratio.

[0525] As used herein, the term "pharmaceutically acceptable" refers to a substance (such as a carrier or diluent) that does not affect the biological activity or properties of the compounds of the present invention and is relatively non-toxic, that is, the substance can be administered to an individual without causing adverse biological reactions or interacting with any component contained in the composition in an adverse manner.

[0526] Those skilled in the art can understand that the compounds of the present disclosure can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; if these compounds contain both an acidic center (such as a carboxyl group) and a basic center (such as an amino group), they can also form inner salts.

[0527] The term "tautomer" refers to functional group isomers resulting from the rapid movement of an atom within a molecule between two positions. The compounds of the present disclosure may exhibit tautomerism. Tautomers of a compound can exist in two or more interconvertible forms. Prototrophic tautomers result from the migration of a hydrogen atom covalently bonded between two atoms. Tautomers generally exist in an equilibrium form, and attempting to isolate a single tautomer usually results in a mixture whose physical and chemical properties are consistent with those of a mixture of compounds. The position of the equilibrium depends on the chemical characteristics within the molecule. For example, in many aliphatic aldehydes and ketones such as acetaldehyde, the keto form predominates; while in phenols, the enol form predominates. The present disclosure encompasses all tautomeric forms of the compounds.

[0528] Depending on their molecular structure, the compounds of the present disclosure can be chiral and thus may exist in various enantiomeric forms. These compounds can therefore exist as racemates or optically active forms. The compounds of the present disclosure encompass isomers or mixtures thereof, racemates, in which each chiral carbon has the R or S configuration. The compounds or intermediates of the present disclosure can be separated into enantiomeric compounds by chemical or physical methods known to those skilled in the art, or can be used in synthesis in this form. In the case of racemic amines, diastereomers are prepared from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids such as tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (such as N-benzoylproline or N-phenylsulfonylproline) or various optically active camphorsulfonic acids in the R and S forms. Chromatographic enantiomeric resolution can also be advantageously carried out with the aid of optically active resolving agents such as dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate or other carbohydrate derivatives or chiral derivatized methacrylate polymers. Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures such as, for example, hexane / isopropanol / acetonitrile. The corresponding stable isomers can be separated according to known methods, for example by extraction, filtration or column chromatography.

[0529] "Isotopes" are all isotopes of atoms that occur in the compounds of the present invention. Isotopes include those atoms having the same atomic number but different mass numbers. Examples of isotopes suitable for incorporation into the compounds of the present invention are hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, for example but not limited to 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 31 P, 32 P, 35 S, 18 F and 36C1. The isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by methods similar to those described in the appended examples using appropriate isotopically labeled reagents in place of the non-isotopically labeled reagents. Such compounds have various potential uses, for example, as standards and reagents in the determination of biological activities. In the case of stable isotopes, such compounds have the potential to advantageously alter biological, pharmacological, or pharmacokinetic properties.

[0530] The term "prodrug" refers to a compound that can be converted into a biologically active compound of the present disclosure under physiological conditions or by solvolysis. The prodrugs of the present disclosure are prepared by modifying the functional groups in the compound, and such modification can be removed by conventional operations or in vivo to obtain the parent compound. Prodrugs include compounds formed by connecting a hydroxyl group or an amino group in the compound of the present disclosure to any group. When the prodrug of the compound of the present disclosure is administered to a mammalian individual, the prodrug is cleaved to form a free hydroxyl group and a free amino group, respectively.

[0531] The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates, and most preferably humans.

[0532] The term "therapeutically effective amount" refers to the amount of an active compound or drug that a researcher, veterinarian, physician, or other clinician is seeking to cause a biological or medical response in a tissue, system, animal, individual, or human, and it includes one or more of the following: (1) Preventing a disease: for example, preventing a disease, disorder, or condition in an individual who is susceptible to the disease, disorder, or condition but has not yet experienced or shown the pathology or symptoms of the disease. (2) Inhibiting a disease: for example, inhibiting a disease, disorder, or condition in an individual who is experiencing or showing the pathology or symptoms of the disease, disorder, or condition (i.e., preventing the further development of the pathology and / or symptoms). (3) Alleviating a disease: for example, alleviating a disease, disorder, or condition in an individual who is experiencing or showing the pathology or symptoms of the disease, disorder, or condition (i.e., reversing the pathology and / or symptoms). Detailed Description of the Invention

[0533] The technical solutions of the present disclosure will be further described in detail below in combination with specific examples. It should be understood that the following examples are only for illustrative explanation of the present disclosure and should not be construed as limiting the protection scope of the present disclosure. All technologies implemented based on the above content of the present disclosure are covered within the scope of protection intended by the present disclosure.

[0534] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0535] List of Abbreviations

[0536] DMF: N,N-Dimethylformamide

[0537] DCM: Dichloromethane

[0538] DIEA: N,N-Diisopropylethylamine

[0539] TEA: Triethylamine

[0540] PE: Petroleum ether

[0541] EA: Ethyl acetate

[0542] MeCN: Acetonitrile

[0543] Et2O: Diethyl ether

[0544] DMSO: Dimethyl sulfoxide

[0545] EtOAc: Ethyl acetate

[0546] THF: Tetrahydrofuran

[0547] TFA: Trifluoroacetic acid

[0548] MeOH: Methanol

[0549] EtOH: Ethanol

[0550] NaH: Sodium hydride

[0551] MeI: Methyl iodide

[0552] EtI: Ethyl iodide

[0553] HFP: 1,1,1,3,3,3-Hexafluoro-2-propanol

[0554] DHP: 3,4-Dihydro-2H-pyran

[0555] PPTS: Pyridinium p-toluenesulfonate

[0556] PPh3: Triphenylphosphine

[0557] DEAD: Diethyl azodicarboxylate

[0558] MsCl: Methanesulfonyl chloride

[0559] TMSOTf: Trimethylsilyl trifluoromethanesulfonate

[0560] m-CPBA: m-Chloroperbenzoic acid

[0561] Analysis Method

[0562] 1. The nuclear magnetic resonance (NMR) spectra were recorded on a 400 MHz Bruker AVANCE III 500 instrument. Chemical shifts were reported in ppm using the deuterated residual solvent as the internal standard. Peak multiplicities were represented as follows: s, singlet; d, doublet; dd, doublet of doublets; t, triplet; dt, triplet of doublets; q, quartet; m, multiplet; br s, broad singlet.

[0563] 2. The purity analysis of the samples was performed on a Waters HPLC / Waters MS system.

[0564] Chromatographic conditions 1:

[0565] Column: Waters X-Bridge-C18 50 mm * 4.6 mm * 3.5 μm

[0566] Column temperature: 40 °C.

[0567] Sample temperature: room temperature

[0568] Detection: UV 214 nm, UV 254 nm

[0569] Flow rate: 2 mL / min: 2 mL / min.

[0570] Mobile phase A: water (0.05% TFA)

[0571] Mobile phase B: MeCN (0.05% TFA)

[0572] Gradient program: B from 5% to 100% for 1.6 minutes, held at 100% for 1.4 minutes.

[0573] Chromatographic conditions 2:

[0574] Column: Waters X Bridge C18 Waters X Bridge C18: 4.6 mm * 50 mm * 3.5 μm

[0575] Column temperature: 40 °C.

[0576] Sample temperature: room temperature

[0577] Detection: UV 214 nm, UV 254 nm

[0578] Flow rate: 2 mL / min: 2 mL / min.

[0579] Mobile phase A: water (0.01 mol / L NH4HCO3) B: MeCN [[ID=5३]]

[0580] Mobile phase B: MeCN

[0581] Gradient program: B from 5% to 100% for 1.6 minutes, hold at 100% for 1.4 minutes.

[0582] 3. Preparative HPLC was performed on a Gilson 281.

[0583] Flow rate: 20 mL / min: 20 mL / min.

[0584] Column: X-Select 10 μm 19X-Select 10 μm 19 * 250 mm column

[0585] Wavelength: 254 nM or 214 nM

[0586] Solvent A water (10 mM NH4HCO3) and solvent B MeCN.

[0587] Example 1: Synthesis example

[0588]

[0589] 1. Synthesis scheme:

[0590]

[0591] 2. Experimental part: 2.1

[0593] (S)-4-(5-chloropyrimidin-2-yl)-3-(cyanomethyl)piperazine-1-carboxylic acid tert-butyl ester (02010-1)

[0594]

[0595] At room temperature, tert-butyl 3-(cyanomethyl)piperazine-1-carboxylate (100 mg, 0.671 mmol) was added to a solution of 2,5-dichloropyrimidine (66 mg, 0.671 mmol) and DIEA (346.4 mg, 2.685 mmol) in NMP (3 mL). The mixture was then stirred at 100 °C overnight, water (10 mL) was added, and the mixture was extracted twice with DCM (10 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 to 1 / 4, silica gel - CS 12 g, 30 mL / min, silica gel, UV 254) to obtain a yellow solid product (46 mg, yield 30.7%).

[0596] ESI-MS m / z calcd for [C 15 H 20 ClN5O2][M - 56 + H] +: 282.1; found: 282.2 2.2

[0598] 2 - ((S)-1-(5-chloropyrimidin-2-yl)-4-((R)-4-((1-(hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-2-yl)acetonitrile (MX02010)

[0599]

[0600] tert-Butyl (S)-4-(5-chloropyrimidin-2-yl)-3-(cyanomethyl)piperazine-1-carboxylate (60 mg, 0.178 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (51 mg, 0.178 mmol) in a solution of HFP (3 mL) were stirred at 120 °C for 2 h under microwave conditions. Then water (10 mL) was added to the mixture, and the mixture was extracted twice with DCM (10 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to obtain a white solid compound (16.6 mg, yield 19.1%).

[0601] ESI-MS m / z calcd for [C 21 H 25 ClN8O2S][M + H] + : 489.2; found: 489.0

[0602] 1 H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 2H), 7.49 (s, 1H), 5.11 (s, 1H), 4.82 (t, J = 5.2 Hz, 1H), 4.61–4.47 (m, 3H), 3.76–3.68 (m, 2H), 3.46–3.35 (m, 1H), 3.30–3.16 (m, 2H), 3.10–3.05 (m, 1H), 2.98–2.80 (m, 4H), 2.46–(m, 5H), 1.82–1.71 (m, 2H),

[0603]

[0604] 1. Synthetic scheme:

[0605]

[0606] 2. Experimental Section: 2.1

[0608] tert-Butyl 3-((5-chloropyrimidin-2-yl)oxy)azetidine-1-carboxylate (02019-1)

[0609]

[0610] To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (500 mg, 2.89 mmol) in THF (8 mL) was added 2,5-dichloropyrimidine (430 mg, 2.89 mmol) and t-BuOK (647 mg, 5.78 mmol). The mixture was stirred at 65 °C under nitrogen for 2 h. After the starting material was consumed, the reaction was quenched with water (20 mL) and extracted three times with EA (50 mL). The combined organic layers were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting crude product was purified by column chromatography (EA / PE = 0 / 1 - 1 / 1, silica gel - CS20 g, 30 mL / min, silica gel, UV 254) to give a white solid product (360 mg, yield 44%).

[0611] ESI-MS m / z calcd for [C 12 H 16 ClN3O3][M - 56 + H] + : 230.1; found: 230.1

[0612] 2.2 2-(Azetidin-3-yloxy)-5-chloropyrimidine (02019-2)

[0613]

[0614] To a solution of tert-butyl 3-((5-chloropyrimidin-2-yl)oxy)azetidine-1-carboxylate (360 mg, 1.26 mmol) in DCM (10 mL) was added TFA (1 mL). The mixture was stirred at room temperature under nitrogen for 3 h. After the reaction was completed, the mixture was distilled under reduced pressure to remove the solvent, giving a white solid product (212 mg, yield 91%).

[0615] ESI-MS m / z calcd for [C7H8ClN3O][M + H] + : 186.0; found: 186.3

[0616] 2.3 (R)-2-(3-((5-Chloropyrimidin-2-yl)oxy)azetidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02019)

[0617]

[0618] To a solution of 2-(azetidin-3-yloxy)-5-chloropyrimidine (100 mg, 0.54 mmol) in 1,4-dioxane (4 mL) was added (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (155 mg, 0.54 mmol) and DIEA (209 mg, 1.62 mmol). The mixture was stirred for 25 minutes under nitrogen protection at 120 °C under microwave conditions. After completion of the reaction, the mixture was distilled under reduced pressure to remove the solvent, and the resulting crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (36.80 mg, yield 16%).

[0619] ESI-MS m / z calcd for [C 18 H 21 ClN6O3S][M+H] + : 437.1; found: 437.0

[0620] 1 H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 7.49 (s, 1H), 5.43–5.38 (m, 1H), 4.86 (t, J = 5.6 Hz, 1H), 4.42 (dd, J = 10.0, 6.4 Hz, 2H), 4.00 (d, J = 7.2 Hz, 2H), 3.73–3.66 (m, 2H), 3.45–3.37 (m, 1H), 3.25–3.17 (m, 1H), 2.97–2.85 (m, 2H), 2.38–2.25 (m, 2H), 2.14–2.10 (m, 2H), 1.82–1.68 (m, 2H).

[0621]

[0622] 1. Synthetic scheme:

[0623]

[0624] 2. Experimental section: 2.1

[0626] tert-Butyl 5-(5-chloropyrimidin-2-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (02020-1)

[0627]

[0628] To a solution of tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate compound (100 mg, 0.51 mmol) in DMF (3 mL), 2,5-dichloropyrimidine (76 mg, 0.51 mmol) and K2CO3 (211 mg, 1.53 mmol) were added. The mixture was stirred at 100 °C under nitrogen protection for 1 hour. Water (20 mL) was added to the mixture, and the mixture was extracted three times with EA (30 mL). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The obtained crude product was purified by column chromatography (EA / PE = 0 / 1 - 1 / 1, silica gel - CS20 g, 30 mL / min, silica gel, UV 254) to obtain a white solid product (140 mg, yield 90%).

[0629] ESI-MS m / z calcd for [C 14 H 19 ClN4O2][M - 56 + H] + : 255.1; found: 255.2 2.2

[0631] 2-(5-chloropyrimidin-2-yl)-2,5-diazabicyclo[4.1.0]heptane (02020-2)

[0632]

[0633] To a solution of tert-butyl 5-(5-chloropyrimidin-2-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate compound (140 mg, 0.45 mmol) in DCM (5 mL), TFA (0.5 mL) was added. The reaction mixture was stirred at room temperature under nitrogen protection for 3 hours. After the starting material was consumed, the mixture was concentrated to dryness under reduced pressure to obtain a white solid product (90 mg, yield 95%).

[0634] ESI-MS m / z calcd for [C9H 11 ClN4][M + H] + : 211.1; found: 211.3 2.3

[0636] (5R)-2-(5-(5-chloropyrimidin-2-yl)-2,5-diazabicyclo[4.1.0]heptan-2-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02020)

[0637]

[0638] To a solution of 2-(5-chloropyrimidin-2-yl)-2,5-diazabicyclo[4.1.0]heptane (90 mg, 0.43 mmol) in 1,4-dioxane (4 mL) was added (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (123 mg, 0.43 mmol) and DIEA (165 mg, 1.28 mmol). The mixture was stirred for 25 minutes under nitrogen protection at 120 °C under microwave conditions. After consumption of the starting materials, the mixture was concentrated under reduced pressure to remove the solvent, and the resulting crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (19.09 mg, yield 10%).

[0639] ESI-MS m / z calcd for [C 20 H 24 ClN7O2S][M+H] + : 462.1; found: 462.0

[0640] 1 H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 2H), 7.47–7.46 (m, 1H), 4.84 (t, J = 6.0 Hz, 1H), 3.98–3.53 (m, 7H), 3.45–3.41 (m, 2H), 3.26–3.19 (m, 1H), 3.00–2.96 (m, 1H), 2.91–2.86 (m, 1H), 2.39–2.33 (m, 2H), 2.18–2.17 (m, 2H), 1.83–1.70 (m, 2H), 1.16–1.15 (m, 1H), 0.42–0.36 (m, 1H),.

[0641]

[0642] 1. Synthetic scheme:

[0643]

[0644] 2. Experimental section: 2.1

[0646] tert-Butyl 4-(5-chloropyrimidin-2-yl)-4,7-diazaspiro[2.5]octane-7-carboxylate (02021-1)

[0647]

[0648] A mixture of 2,5-dichloropyrimidine (200 mg, 1.34 mmol), tert-butyl 4,7-diazaspiro[2.5]octane-7-carboxylate (711 mg, 3.35 mmol) and DIEA (1.1 mL, 6.7 mmol) in n-butanol (10 mL) was stirred under microwave conditions at 150 °C under argon protection for 2 h. After the mixture was cooled, the solvent was removed by distillation under reduced pressure. The crude product was purified by column chromatography (EA / PE = 0 - 1 / 19, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254) to obtain a colorless oily product (71 mg, yield 16.3%).

[0649] ESI-MS m / z calcd for [C 15 H 21 ClN4O2][M-56+H] + : 269.1; found: 268.9 2.2

[0651] (R)-2-(4-(5-chloropyrimidin-2-yl)-4,7-diazaspiro[2.5]octane-7-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02021)

[0652]

[0653] tert-Butyl 4-(5-chloropyrimidin-2-yl)-4,7-diazaspiro[2.5]octane-7-carboxylate (44 mg, 0.11 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (32 mg, 0.11 mmol) in HFP (3 mL) were stirred at 120 °C for 2 h under microwave conditions. After the mixture was cooled, the solvent was removed by distillation under reduced pressure. The crude product was purified by reverse-phase column (MeCN / H2O = 0 - 12 / 13, C-18 column, 50 mL / min, UV 214) to obtain the crude product (20 mg), and then the crude product was further purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain the white solid product (11.48 mg, yield 17.8%).

[0654] ESI-MS m / z calcd for[C 21 H 26 ClN7O2S][M+H] + : 476.2; found: 475.8

[0655] 1 H NMR (400 MHz, DMSO-d6) δ 8.52 (s, 2H), 7.41–7.38 (m, 1H), 4.85 (t, J = 5.6 Hz, 1H), 3.95–3.93 (m, 2H), 3.83–3.66 (m, 6H), 3.40–3.37 (m, 1H), 3.24–3.16 (m, 1H), 2.95–2.83 (m, 2H), 2.33–2.12 (m, 4H), 1.77–1.73 (m, 2H), 0.95–0.89 (m, 4H).

[0656]

[0657] 1. Synthetic scheme:

[0658]

[0659] 2. Experimental section: 2.1

[0661] 5-Iodo-1-(triisopropylsilyl)-1H-indole (02024-1)

[0662]

[0663] At 0 °C, a solution of 5-iodo-1H-indole (1.7 g, 6.99 mmol) in anhydrous THF (20 mL) was added dropwise to a solution of NaH (60%, 364 mg, 9.09 mmol) in THF (20 mL). The mixture was slowly warmed to room temperature over 30 minutes. Then, chlorotriisopropylsilane (1.75 g, 9.09 mmol) was added dropwise within 5 minutes. The resulting mixture was slowly warmed to room temperature and stirred until the starting material was consumed as monitored by TLC. After completion of the reaction, the reaction mixture was quenched with saturated aqueous NH4Cl (20 mL) at 0 °C and extracted three times with Et2O (15 mL). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 - 10%, silica gel - CS 40 g, 50 mL / min, silica gel, UV 254) to give the product as a colorless oil (2.1 g, yield 75.17%).

[0664] ESI-MS m / z calcd for[C 17 H 26 INSi]

[0665] 1 H NMR(400MHz,Chloroform-d)δ7.95(d,J=1.6Hz,1H),7.38(dd,J=8.4,1.6Hz,1H),7.29–7.26(m,1H),7.20(d,J=3.2Hz,1H),6.54(d,J=2.8Hz,1H),1.71–1.63(m,3H),1.14–1.12(m,18H). 2.2

[0667] tert-Butyl 3-(1-(triisopropylsilyl)-1H-indol-5-yl)azetidine-1-carboxylate (02024-2)

[0668]

[0669] In a nitrogen atmosphere, zinc powder (327 mg, 5.01 mmol) was vigorously stirred in a solution of DMA (1.6 mL) and heated to 65 °C. Subsequently, TMSCl (65 mg, 0.6 mmol) and dibromoethane (113 mg, 0.6 mmol) were added, and then the mixture was stirred at 65 °C for another 30 minutes. At 65 °C, the solution prepared above was added dropwise to a solution of tert-butyl 3-iodoazetidine-1-carboxylate (851 mg, 3.0 mmol) in DMA (2 mL), and then the reaction mixture was cooled to room temperature. A solution of 5-iodo-1-(triisopropylsilyl)-1H-indole (800 mg, 2.0 mmol) in DMA (4 mL) was added. Subsequently, Pd(dppf)Cl2 (44 mg, 0.06 mmol) and CuI (23 mg, 0.12 mmol) were added. The reaction mixture was heated to 80 °C and stirred for 2 hours, cooled to room temperature, quenched with water (150 mL), then NH4Cl (2 g) was added, and it was extracted twice with Et2O (150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by column chromatography (EA / PE = 0 - 10%, silica gel - CS 40 g, 50 mL / min, silica gel, UV 254) to obtain a white solid product (0.7 g, yield 81.52%).

[0670] ESI-MS m / z calcd for[C 25 H 40 N2O2Si][M+H] + : 429.3; found: 429.2 2.3

[0672] tert-Butyl 3-(1H-indol-5-yl)azetidine-1-carboxylate (02024-3)

[0673]

[0674] To a solution of tert-butyl 3-(1-(triisopropylsilyl)-1H-indol-5-yl)azetidine-1-carboxylate (0.7 g, 1.64 mmol) in THF (10 mL) was added TBAF (1 M THF solution, 3.27 mL). The mixture was stirred at room temperature for 2 hours, quenched with water (30 mL), and then extracted twice with EA (30 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated, and the crude product was purified by column chromatography (EA / PE = 0 - 30%, silica gel - CS25 g, 30 mL / min, silica gel, UV254) to obtain a white solid product (401 mg, yield 90.03%).

[0675] ESI-MS m / z calcd for[C16 H 20 N2O2][M - 56 + H] + : 217.2; found: 217.2 2.4

[0677] (R)-2-(3-(1H-Indol-5-yl)azetidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02024)

[0678]

[0679] A mixture of tert-butyl 3-(1H-indol-5-yl)azetidine-1-carboxylate (100 mg, 0.37 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (104 mg, 0.37 mmol) in HFP (3 mL) was stirred at 120 °C for 2 h under microwave conditions. After completion of the reaction, the mixture was distilled under reduced pressure to remove the solvent, and the crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give a white solid product (58 mg, yield 37.3%).

[0680] ESI-MS m / z calcd for [C 22 H 25 N5O2S][M + H] + : 424.2; found: 424.0

[0681] 1 H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 7.50 (s, 1H), 7.41–7.37 (m, 2H), 7.32 (t, J = 2.8 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.39 (s, 1H), 4.88 (t, J = 5.6 Hz, 1H), 4.46–4.42 (m, 2H), 4.03–3.94 (m, 3H), 3.71–3.70 (m, 2H), 3.44–3.38 (m, 1H), 3.26–, 3. Y, 2.98–2.85 (m, 2H), 2.39–2.31 (m, 2H), 2.15–2.10 (m, 2H), 1.80–1.70 (m, 2H).

[0682]

[0683] 1. Synthetic Scheme:

[0684]

[0685] 2. Experimental Section: 2.1

[0687] (R)-tert-Butyl 3-((1H-indol-6-yl)oxy)pyrrolidine-1-carboxylate (02025-1)

[0688]

[0689] To a solution of 1H-indol-6-ol (171 mg, 1.284 mmol) and (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (200 mg, 1.07 mmol) in 1,4-dioxane (20 mL) was added CMBP (0.75 mL, 3.21 mmol). The mixture was stirred overnight under argon protection at 100 °C. After cooling, the solvent was removed by distillation under reduced pressure. The crude product was purified by reverse-phase column chromatography (MeCN / H2O = 1 / 9 - 11 / 9, C-18 column, 50 mL / min, UV 214) to give a brown oily product (322 mg, yield 99.7%).

[0690] ESI-MS m / z calcd for [C 17 H 22 N2O3][M - 56 + H] + : 247.2; found: 247.0 2.2

[0692] (R)-6-(Pyrrolidin-3-yloxy)-1H-indole (02025-2)

[0693]

[0694] A solution of (R)-tert-butyl 3-((1H-indol-6-yl)oxy)pyrrolidine-1-carboxylate (200 mg, 0.66 mmol) in HFP (5 mL) was stirred under argon protection at 120 °C for 10 h under microwave irradiation. After cooling, the solvent was removed by distillation under reduced pressure to give a brown oily crude product (133 mg, yield 99.4%) which was directly used in the next step.

[0695] ESI-MS m / z calcd for [C 12 H 14 N2O][M + H] + : 203.1; found: 203.2 2.3

[0697] (R)-2-((R)-3-((1H-Indol-6-yl)oxy)pyrrolidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02025)

[0698]

[0699] To a solution of (R)-6-(pyrrolidin-3-yloxy)-1H-indole (44 mg, 0.22 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (63 mg, 0.22 mmol) in DMF (10 mL) was added DIEA (0.18 mL, 1.1 mmol). The mixture was then stirred overnight at 80 °C under argon protection. After cooling, the mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 9, silica gel - CS20 g, 20 mL / min, UV254) to obtain a crude product (50 mg). The crude product was then further purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (33.02 mg, yield 33.5%).

[0700] ESI-MS m / z calcd for [C 23 H 27 N5O3S][M + H] + : 454.2; found: 454.0

[0701] 1 H NMR (400 MHz, DMSO-d6) δ 10.88 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 7.2 Hz, 1H), 7.20 (s, 1H), 6.91 (s, 1H), 6.66 (d, J = 8.8 Hz, 1H), 6.33 (s, 1H), 5.08 (s, 1H), 4.89 - 4.84 (m, 1H), 3.81 - 3.69 (m, 5H), 3.60 - 3.51 (m, 1H), 3.46 - 3.37 (m, 1H), 3.25 - 3.15 (m, 1H), 2.98 - 2.80 (m, 2H), 2.41 - 2.29 (m, 2H), 2.22 - 2.05 (m, 4H), 1.81 - 1.66 (m, 2H).

[0702]

[0703] 1. Synthetic Scheme:

[0704]

[0705] 2. Experimental Section: 2.1

[0707] tert-Butyl 5-(1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole-1-carboxylate (02026-1)

[0708]

[0709] A reaction mixture of tert-butyl 5-bromo-1H-indole-1-carboxylate (1 g, 3.38 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate (1 g, 3.38 mmol), Pd(dppf)Cl2 (247 mg, 0.338 mmol), K2CO3 (1.4 g, 10.14 mmol) and water (16 mL) in 1,4-dioxane (80 mL) was stirred overnight under argon protection at 100 °C. After cooling, the reaction mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0-1 / 9, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254), and a white solid product (960 mg, yield 73.9%) was obtained.

[0710] ESI-MS m / z calcd for [C 22 H 28 N2O4][M - 56 + H] + : 329.2; found: 329.2 2.2

[0712] tert-Butyl 5-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-1H-indole-1-carboxylate (02026-2)

[0713]

[0714] To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole-1-carboxylate (300 mg, 0.34 mmol) in DCM (30 mL) and MeOH (75 mL) was added Pd(OH)2 (30 mg), and the mixture was stirred at room temperature for 12 minutes under a hydrogen atmosphere. After completion of the reaction, the mixture was filtered under reduced pressure, and the resulting filtrate was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0 - 1 / 9, silica gel - CS20 g, 20 mL / min, silica gel, UV 254) to give a colorless oily product (260 mg, yield 86.2%).

[0715] ESI-MS m / z calcd for[C 22 H 30 N2O4][M-112+H] + :275.2;found:275.2 2.3

[0717] 5-(Pyrrolidin-3-yl)-1H-indole (02026-3)

[0718]

[0719] To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-1H-indole-1-carboxylate (248 mg, 0.64 mmol) in 1,4-dioxane (10 mL) was added 4N (HCl) / 1,4-dioxane solution (10 mL), and the mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was distilled under reduced pressure to remove the solvent. The crude product was neutralized with DIEA (10 mL), concentrated by distillation under reduced pressure to give a crude red solid product (119 mg, yield 99.9%). It was directly used for the next reaction.

[0720] ESI-MS m / z calcd for[C 12 H 14 N2][M+H] + :187.1;found:187.4 2.4

[0722] (5R)-2-(3-(1H-Indol-5-yl)pyrrolidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02026)

[0723]

[0724] To a solution of 5-(pyrrolidin-3-yl)-1H-indole (130 mg, 0.5 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (144 mg, 0.5 mmol) in 1,4-dioxane (10 mL) was added DIEA (0.41 mL, 2.5 mmol). The mixture was stirred at 120 °C for 2 h under microwave conditions. After cooling, the mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 9, silica gel - CS20 g, 20 mL / min, UV254) to give a crude product (50 mg), which was then further purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give a white solid product (4.69 mg, yield 2.1%).

[0725] ESI-MS m / z calcd for [C 23 H 27 N5O2S][M + H] + : 438.2; found: 438.0

[0726] 1 H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 7.46 (d, J = 4.0 Hz, 1H), 7.36–7.28 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 6.37 (s, 1H), 4.90–4.84 (m, 1H), 4.05–3.95 (m, 1H), 3.82–3.67 (m, 3H), 3.56–3.39 (m, 4H), 3.24–3.17 (m, 1H), 2.95–2.86 (m, 2H), 2.46–2.27 (m, 3H), 2.18–2.04 (m, 3H), 1.79–1.66 (m, 2H).

[0727]

[0728] 1. Synthetic Scheme:

[0729]

[0730] 2. Experimental Section: 2.1

[0732] 2-Chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one (02029-1)

[0733]

[0734] To a solution of 2,4-dichloro-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one (23 mg, 0.105 mmol) in MeCN (4 mL) was added (1-aminocyclobutyl)methanol (11.7 mg, 0.115 mmol) and TEA (1 mL). The mixture was stirred overnight at 70 °C, and the mixture was concentrated by distillation under reduced pressure. The crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 10, silica gel - CS 4 g, 20 mL / min, silica gel, UV 254) to give a yellow solid product (purity 80%, 28.0 mg, yield 98.0%).

[0735] ESI-MS m / z calcd for[C 12 H 15 ClN4O2][M+H] + : 283.1; found: 283.1 2.2

[0737] 2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one (MX02029)

[0738]

[0739] (2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one (purity 80%, 28.0 mg, 0.08 mmol) and tert-butyl 4-(5-chloropyrimidin-2-yl)piperidine-1-carboxylate (45 mg, 0.15 mmol) in a mixture of HFP (3 mL) was stirred at 120 °C for 2 hours under microwave conditions. The reaction mixture was concentrated by distillation under reduced pressure to remove the solvent, and the crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254) to give a white solid product (2.0 mg, yield 4.55%).

[0740] ESI-MS m / z calcd for[C 21 H 26 ClN7O2][M+H] + : 444.2; found: 444.0

[0741] 11H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 8.87 (s, 2H), 7.43 (s, 1H), 4.83 (t, J = 6.0 Hz, 1H), 4.72 (d, J = 10.0 Hz, 2H), 3.69 (d, J = 5.2 Hz, 2H), 3.33–3.26 (m, 2H), 3.21–3.14 (m, 1H), 3.05–2.99 (m, 2H), 2.62 (t, J = 6.8 Hz, 2H), 2.26–2.11 (m, 4H), 1.96 (d, J = 10.4 Hz, 2H), 1.83–1.74 (m, 2H), 1.67–1.59 (m, 2H),

[0742]

[0743] 1. Synthetic Scheme:

[0744]

[0745] 2. Experimental Section: 2.1

[0747] (1 - ((2 - Chloropyrido[3,2 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (02035 - 1)

[0748]

[0749] To a solution of (1 - aminocyclobutyl)methanol (50.5 mg, 0.5 mmol) and DIEA (0.1 mL, 0.625 mmol) in THF (5 mL), a solution of 2,4 - dichloropyrido[3,2 - d]pyrimidine (100 mg, 0.5 mmol) in THF (15 mL) was added dropwise within 10 minutes. The resulting mixture was stirred at room temperature overnight under argon protection. After cooling, the reaction mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0 - 1 / 1, silica gel - CS20 g, 20 mL / min, silica gel, UV 254), and a white solid product (105 mg, yield 79.3%) was obtained.

[0750] ESI - MS m / z calcd for [C 12 H 13 ClN4O][M + H] + : 265.1; found: 265.1 2.2

[0752] (1 - ((2 - (4 - (5 - Chloropyrimidin - 2 - yl)piperidin - 1 - yl)pyrido[3,2 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (MX02035)

[0753]

[0754] To a solution of (1 - ((2 - chloropyrido[3,2 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (68 mg, 0.32 mmol) and 5 - chloro - 2 - (piperidin - 4 - yl)pyrimidine (92 mg, 0.32 mmol) in DMF (20 mL) was added DIEA (0.26 mL, 1.6 mmol), and the mixture was stirred at 80 °C overnight under argon protection. After cooling, the mixture was distilled under reduced pressure to remove the solvent, and the crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 9, silica gel - CS20 g, 20 mL / min, UV 254) to obtain a crude product (100 mg). Then the crude product was further purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X - Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (73.60 mg, yield 49.6%).

[0755] ESI - MS m / z calcd for [C 21 H 24 ClN7O][M + H] + : 426.2; found: 426.0

[0756] 1 H NMR (400 MHz, DMSO - d6) δ 8.86 (s, 2H), 8.33 (dd, J = 4.4, 1.6 Hz, 1H), 7.65 (dd, J = 8.4, 1.6 Hz, 1H), 7.57–7.53 (m, 2H), 4.99 (t, J = 5.6 Hz, 1H), 4.83 (d, J = 12.8 Hz, 2H), 3.78 (d, J = 5.6 Hz, 2H), 3.22–3.16 (m, 1H), 3.10–3.04 (m, 2H), 2.64–2.56 (m, 2H), 2.18–2.11 (m, 2H), 1.99 (d, J = 10.4 Hz, 2H), 1.88–1.65 (m, 4H).

[0757]

[0758] 1. Synthetic Scheme:

[0759]

[0760] 2. Experimental Section: 2.1

[0762] tert-Butyl 2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (02036-1)

[0763]

[0764] To a solution of tert-butyl 2,4-dichloro-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (660 mg, 2.17 mmol) in MeCN (15 mL) was added (1-aminocyclobutyl)methanol (219.5 mg, 2.17 mmol) and TEA (658.7 mg, 6.51 mmol). The mixture was heated to 70 °C and stirred for 16 h, cooled to room temperature and concentrated. The crude product was purified by column chromatography (EA / PE = 0 - 50%, silica gel - CS 40 g, 50 mL / min, silica gel, UV light 254) to give the white solid product (441 mg, yield 55.1%).

[0765] ESI-MS m / z calcd for [C 17 H 25 ClN4O3][M + H] + : 369.2; found: 369.0 2.2

[0767] tert-Butyl 2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (02036-2)

[0768]

[0769] To a solution of tert-butyl 2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (441 mg, 1.20 mmol) in DMF (15 mL) was added 5-chloro-2-(piperidin-4-yl)pyrimidine (378 mg, 1.91 mmol) and DIEA (309 mg, 2.39 mmol). The mixture was heated to 120 °C and stirred for 16 h, then the mixture was cooled to room temperature and concentrated to dryness under reduced pressure. The crude product was purified by column chromatography (MeOH / DCM = 0 - 10%, silica gel - CS25 g, 30 mL / min, UV 254) to give the white solid product (101 mg, yield 15.9%).

[0770] ESI-MS m / z calcd for [C 26 H 36 ClN7O3][M + H]+ : 530.3; found: 530.0 2.3

[0772] (1 - ((2 - (4 - (5 - chloropyrimidin - 2 - yl)piperidin - 1 - yl) - 5,6,7,8 - tetrahydropyrido[4,3 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (MX02036)

[0773]

[0774] A solution of tert - butyl 2 - (4 - (5 - chloropyrimidin - 2 - yl)piperidin - 1 - yl) - 4 - ((1 - (hydroxymethyl)cyclobutyl)amino) - 7,8 - dihydropyrido[4,3 - d]pyrimidine - 6(5H) - carboxylate (20 mg, 0.04 mmol) in HFP (3 mL) was stirred at 120 °C for 3.5 h under microwave conditions, then the mixture was cooled to room temperature and concentrated to dryness under reduced pressure. The crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X - Select 10μm 19*250mm, 20 mL / min, UV 254) to give a white solid product (3.6 mg, yield 18.0%).

[0775] ESI - MS m / z calcd for [C 21 H 28 ClN7O][M + H] + : 430.2; found: 430.0

[0776] 1 H NMR (400 MHz, DMSO - d6) δ 8.85 (s, 2H), 5.83 (s, 1H), 4.78 (t, J = 5.6 Hz, 1H), 4.61–4.58 (m, 2H), 3.70 (d, J = 5.6 Hz, 2H), 3.43 (s, 2H), 3.12–3.07 (m, 1H), 2.90–2.85 (m, 4H), 2.36–2.34 (m, 2H), 2.25–2.10 (m, 5H), 1.88–1.85 (m, 2H), 1.77–1.74 (m, 2H), 1.63–1.59 (m, 2H).

[0777]

[0778] 1. Synthetic Scheme:

[0779]

[0780] 2. Experimental Section: 2.1

[0782] 1-(2-(4-(5-Chloropyrimidin-2-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)prop-2-en-1-one (MX02037)

[0783]

[0784] To a solution of (1-((2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)cyclobutyl)methanol (0.189 mmol, crude) in MeOH (5 mL) was added acryloyl chloride (171 mg, 1.89 mmol). The mixture was stirred at room temperature for 16 h and then concentrated to dryness under reduced pressure. The crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give the white solid product (3.20 mg, yield 3.5%).

[0785] ESI-MS m / z calcd for [C 24 H 30 ClN7O2][M+H] + : 484.2; found: 484.0

[0786] 1 H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 2H), 6.99–6.86 (m, 1H), 6.34 (d, J = 11.6 Hz, 1H), 6.17 (dd, J = 28.0, 16.0 Hz, 1H), 5.74 (dd, J = 24.8, 11.2 Hz, 1H), 4.78–4.73 (m, 1H), 4.61 (d, J = 12.8 Hz, 2H), 4.34 (d, J = 14.4 Hz, 2H), 3.75–3.72 (m, 4H), 3.14–3.09 (m, 1H), 2.90 (t, J = 12.0 Hz, 2H), 2.59–2.57 (m, 1H), 2.47–2.45 (m, 1H), 2.33 - 2.17 (m, 4H), 1.89–1.73 (m, 4H), 1.64 - 1.56 (m, 2H).

[0787]

[0788] 1. Synthetic scheme:

[0789]

[0790] 2. Experimental section: 2.1

[0792] tert-Butyl 2-(1-((benzyloxy)carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (02040-1)

[0793]

[0794] A mixture of tert-butyl 2-chloro-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (300 mg, 1.11 mmol), benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (381 mg, 1.11 mmol), Pd(dppf)Cl2 (81 mg, 0.111 mmol), K2CO3 (460 mg, 3.33 mmol) and water (0.8 mL) in 1,4-dioxane (4 mL) was stirred overnight under argon at 100 °C. After cooling, the reaction mixture was concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0–1 / 3, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254), and a yellow oily product (501 mg, yield 99.9%) was obtained.

[0795] ESI-MS m / z calcd for[C 25 H 30 N4O4][M-56+H] + : 451.2; found: 451.3 2.2

[0797] tert-Butyl 2-(piperidin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (02040-2)

[0798]

[0799] To a solution of tert-butyl 2-(1-((benzyloxy)carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (393 mg, 0.87 mmol) in EA (30 mL) was added Pd / C (80 mg). The mixture was stirred overnight under a hydrogen atmosphere at room temperature. After the reaction was completed, the mixture was filtered under reduced pressure, and the resulting filtrate was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0 - 1 / 3, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254) to obtain a colorless oily product (277 mg, yield 99.7%).

[0800] ESI-MS m / z calcd for[C 17 H 26 N4O2][M+H] + :319.2;found:319.2 2.3

[0802] (R)-tert-Butyl 2-(1-(4-((1-(hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperidin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (02040-3)

[0803]

[0804] To a mixture of tert-butyl 2-(piperidin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (277 mg, 0.87 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (280 mg, 0.87 mmol) in 1,4-dioxane (10 mL) was added DIEA (0.43 mL, 2.61 mmol), and the mixture was stirred for 1 hour under argon protection at 120 °C under microwave conditions. After cooling, the mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 9, silica gel - CS 20 g, 20 mL / min, UV 254) to obtain a yellow solid product (495 mg, yield 99.9%).

[0805] ESI-MS m / z calcd for[C 28 H 39 N7O4S][M+H] + :570.3;found:569.8 2.4

[0807] (R)-4-((1-(Hydroxymethyl)cyclobutyl)amino)-2-(4-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)piperidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02040)

[0808]

[0809] (R)-tert-Butyl 2-(1-(4-((1-(hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperidin-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (150 mg, 0.26 mmol) in a mixture of HFP (10 mL) was stirred under argon at 120 °C for 2 h under microwave conditions. After cooling, the mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the product as a white solid (49.00 mg, yield 39.6%).

[0810] ESI-MS m / z calcd for [C 23 H 31 N7O2S][M+H] + : 470.2; found: 470.0

[0811] 1 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.36 (s, 1H), 4.85 (t, J = 5.6 Hz, 1H), 4.71 (d, J = 12.4 Hz, 2H), 3.79 (s, 2H), 3.73–3.71 (m, 2H), 3.45–3.37 (m, 1H), 3.24–3.17 (m, 1H), 3.09–2.83 (m, 8H), 2.69 (t, J = 6.0 Hz, 2H), 2.39–2.25 (m, 2H), 2.18–2.12 (m, 2H), 1.91–1.88 (m, 2H), 1.79–1.73 (m, 2H), 1.65–1.61 (m, 2H).

[0812]

[0813] 1. Synthetic scheme:

[0814]

[0815] 2. Experimental section: 2.1

[0817] (1 - ((2 - chloro - 6,7 - dihydrothieno[3,2 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (02043 - 1)

[0818]

[0819] To a solution of 2,4 - dichloro - 6,7 - dihydrothieno[3,2 - d]pyrimidine (6.641 g, 32.07 mmol) in MeCN (50 mL) was added (1 - aminocyclobutyl)methanol (3.244 g, 32.07 mmol) and TEA (20 mL). After the mixture was stirred at 75 °C for 16 h, the solvent was removed by distillation under reduced pressure. The crude product was purified by column chromatography (EA / DCM = 0 - 60%, silica - CS 120 g, 50 mL / min, silica, UV 254) to give a yellow solid product (4.01 g, yield 46.1%).

[0820] ESI - MS m / z calcd for [C 11 H 14 ClN3OS][M + H] + : 272.1; found: 272.1 2.2

[0822] (R) - 2 - chloro - 4 - ((1 - (hydroxymethyl)cyclobutyl)amino)-6,7 - dihydrothieno[3,2 - d]pyrimidine 5 - oxide (02043 - 2)

[0823]

[0824] To a solution of (1 - ((2 - chloro - 6,7 - dihydrothieno[3,2 - d]pyrimidin - 4 - yl)amino)cyclobutyl)methanol (3.5 g, 12.88 mmol) and S - 1,1'-bi - 2 - naphthol (369.0 mg, 1.288 mmol) in DCM (60 mL) were added titanium(IV) isopropoxide (182.0 mg, 0.64 mmol) and water (232.0 mg, 12.88 mmol). After the mixture was stirred at room temperature for 1 h, 70% aqueous tert - butyl hydroperoxide (2 g, 14.17 mmol) was added in one portion. Then the mixture was stirred at room temperature for 2 h, water (50 mL) was added, and the mixture was extracted three times with DCM (60 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (DCM / MeOH = 1 / 0 - 10 / 1, Silica - CS 80 g, 50 mL / min, silica, UV 254) to give a yellow solid product (3.50 g, yield 94.6%).

[0825] ESI-MS m / z calcd for [C 11 H 14 ClN3O2S][M+H] + : 288.0; found: 288.0

[0826] 1 H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 4.89 (t, J = 5.6 Hz, 1H), 3.74–3.66 (m, 2H), 3.61–3.52 (m, 1H), 3.38–3.30 (m, 1H), 3.16–3.12 (m, 1H), 3.05–2.99 (m, 1H), 2.32–2.17 (m, 4H), 1.81–1.71 (m, 2H). 2.3

[0828] (R)-2-(4,5-Dihydro-2H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02043)

[0829]

[0830] (R)-2-Chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (57 mg, 0.2 mmol) in DMF (5 mL) was added to 4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine hydrochloride (38 mg, 0.24 mmol) and DIEA (1.5 mL). The reaction mixture was stirred at 80 °C for 4 h, the solvent was removed by distillation under reduced pressure, and the crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV254] to give the white solid product (20.0 mg, yield 26.9%).

[0831] ESI-MS m / z calcd for [C 17 H 22 N6O2S][M+H] + : 375.2; found: 375.0

[0832] 11H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 7.47 (s, 1H), 7.41 (s, 1H), 4.88–4.83 (m, 3H), 3.96 (br, 2H), 3.78–3.71 (m, 2H), 3.46–3.38 (m, 1H), 3.24–3.16 (m, 1H), 2.94 (dd, J=16.8, 8.0 Hz, 1H), 2.86 (dd, J=14.4, 7.2 Hz, 1H), 2.67–2.61 (m, 2H), 2.40–2.27 (m, 2H), 2.21–2.17 (m, 2H), 1.82–1.74 (m, 2H).

[0833]

[0834] 1. Synthesis Scheme:

[0835]

[0836] 2. Experimental Section: 2.1

[0838] tert-Butyl 2-chloro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (02044-1)

[0839]

[0840] Zinc powder (338 mg, 5.17 mmol) was added to a solution of tert-butyl 2,4-dihydro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (300 mg, 1.03 mmol) in MeOH (10 mL) and AcOH (1 mL). Then the mixture was stirred overnight at 50 °C. The mixture was distilled under reduced pressure to remove the solvent, water (20 mL) was added, and the mixture was extracted three times with DCM (20 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 - 1 / 1, silica gel - CS20 g, 40 mL / min, silica gel, UV 254) to obtain a yellow oily product (202.0 mg, yield 84.8%).

[0841] ESI-MS m / z calcd for [C 11 H 14 ClN3O2][M + H] + : 256.1; found: 256.2 2.2

[0843] tert-Butyl 2-(1-((benzyloxy)carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (02044-2)

[0844]

[0845] To a solution of tert-butyl 2-chloro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (200 mg, 0.782 mmol) in 1,4-dioxane (5 mL) and water (1 mL) were added benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (322 mg, 0.94 mmol), K2CO3 (324 mg, 2.35 mmol), and Pd(dppf)Cl2 (32 mg, 0.04 mmol). The mixture was stirred overnight under nitrogen at 100 °C. After completion of the reaction, the mixture was concentrated under reduced pressure to remove the solvent. Water (20 mL) was added, and the mixture was extracted three times with DCM (20 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 to 1 / 1, silica gel - CS 20 g, 40 mL / min, UV 254) to give a white solid product (255.0 mg, yield 74.6%).

[0846] ESI-MS m / z calcd for [C 24 H 28 N4O4][M+H] + : 437.2; found: 437.2 2.3

[0848] tert-Butyl 2-(piperidin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (MX02044-3)

[0849]

[0850] To a solution of tert-butyl 2-(1-((benzyloxy)carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (255 mg, 0.584 mmol) in MeOH / THF (v / v = 1:1, 10 mL) was added Pd / C (50 mg, 0.256 mmol). The mixture was stirred overnight under a hydrogen atmosphere at room temperature. The mixture was filtered and concentrated to give a yellow solid product (200 mg, 0.584 mmol, yield: 100%).

[0851] ESI-MS m / z calcd for [C 16 H 24 N4O2][M+H] + : 305.2; found: 305.2 2.4

[0853] (R)-tert-Butyl 2-(1-(4-((1-(hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperidin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (02044-4)

[0854]

[0855] To a solution of (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (90 mg, 0.313 mmol) in DMF (5 mL) and DIEA (1 mL) was added tert-butyl 2-(piperidin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (200 mg, 0.584 mmol). The reaction mixture was stirred at 115 °C for 3 h, and the reaction mixture was concentrated by distillation under reduced pressure. The crude product was purified by column chromatography (MeOH / DCM = 0 / 1 to 1 / 10, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254) to give the yellow solid product (165.0 mg, yield 95.0%).

[0856] ESI-MS m / z calcd for [C 27 H 37 N7O4S][M+H] + : 556.3; found: 556.2 2.5

[0858] (R)-2-(4-(6,7-Dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)piperidin-1-yl)-4-((1-

[0859] (hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine-5-oxide (MX02044)

[0860]

[0861] (R)-tert-Butyl 2-(1-(4-((1-(hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperidin-4-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (50 mg, 0.09 mmol) in a mixture of HFP (2 mL) was stirred at 120 °C for 2 h under microwave conditions. The mixture was distilled under reduced pressure to remove the solvent, and the crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (10.05 mg, yield 24.4%).

[0862] ESI-MS m / z calcd for[C 22 H 29 N7O2S][M+H] + : 456.2; found: 456.0

[0863] 1 1H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 1H), 7.39 (s, 1H), 4.86 (t, J = 5.6 Hz, 1H), 4.71 (d, J = 12.0 Hz, 2H), 4.58–4.5l (m, 1H), 4.08 (s, 2H), 3.98 (s, 2H), 3.70–3.68 (m, 2H), 3.45–3.37 (m, 1H), 3.24–3.12 (m, 2H), 3.07–2.98 (m, 2H), 2.96–2.28 (m, 2H), 2.38–2.25 (m, 2H), 2.18–2.13 (m, 2H), 1.94–1.91 (m, 2H),, 1.82–1.60 (m, 4H).

[0864]

[0865] 1. Synthetic scheme:

[0866]

[0867] 2. Experimental section: 2.1

[0869] 4,4-Dimethyl-2-oxocyclohexanecarbaldehyde (02053-1)

[0870]

[0871] At 30 °C, ethyl formate (1.2 g, 16.24 mmol) was added to a solution of NaH (60%, 349 mg, 8.72 mmol) in THF (10 mL), and the mixture was stirred for 1 hour. Then, at 35 °C, ethyl formate (1.2 g, 16.24 mmol) was added to the reaction solution, and the mixture was stirred overnight at 40 °C. The mixture was acidified to pH 3 with 1N aqueous HCl, and then extracted twice with EA (50 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give a yellow oil (990 mg, yield 81.1%).

[0872] ESI-MS m / z calcd for[C9H 14 O2][M+H] + :155.1; found:155.4 2.2

[0874] 6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (02053-2)

[0875]

[0876] Hydrazine hydrate (82 mg, 1.64 mmol) in MeOH (5 mL) was added dropwise to a solution of 4,4-dimethyl-2-oxocyclohexanecarbaldehyde (250 mg, 1.62 mmol) in MeOH (10 mL). The mixture was heated under reflux for 15 minutes. After cooling, the solvent was removed by distillation under reduced pressure, water (20 mL) was added, and the mixture was extracted with EA (20 mL). The organic layer was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give a yellow oil (135 mg, yield 55.4%).

[0877] ESI-MS m / z calcd for[C9H 14 N2][M+H] + :151.1; found:151.4 2.3

[0879] 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (02053-3)

[0880]

[0881] At room temperature, I2 (3.68 g, 8.7 mmol) and KOH (967 mg, 17.23 mmol) were added to a solution of 6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (523 mg, 3.48 mmol) in DMF (10 mL). Then the mixture was stirred at room temperature for 4 hours. The reaction was cooled in an ice bath, and an aqueous solution of NaHSO3 (2 g in 20 mL of water) was added dropwise. Then more water (100 mL) was added, and a precipitate appeared. After filtration, a yellow solid product (400 mg, yield 41%) was obtained.

[0882] ESI-MS m / z calcd for[C9H 13 IN2][M+H] + :277.0; found:277.1 2.4

[0884] Benzyl 4-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (02053-4)

[0885]

[0886] To a solution of 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (229 mg, 0.83 mmol) and benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (285 mg, 0.83 mmol) in 1,4-dioxane / water (12 mL, v / v 3:1) were added Pd(dppf)Cl2 (18 mg, 0.02 mmol) and K2CO3 (344 mg, 2.49 mmol). The mixture was stirred under nitrogen at 60 °C for 3 hours. Then water (20 mL) was added, and the mixture was extracted with EA (20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (PE / EA = 0 - 1, silica gel - CS20 g, 30 mL / min, silica gel, UV 254) to obtain a white solid product (164 mg, yield 54.0%).

[0887] ESI-MS m / z calcd for[C 23 H 28 N2O2][M+H] + :365.2; found:366.2 2.5

[0889] 6,6-Dimethyl-3-(piperidin-4-yl)-4,5,6,7-tetrahydro-1H-indazole (02053-5)

[0890]

[0891] To a solution of benzyl 4-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (210 mg, 0.57 mmol) in MeOH (3 mL) was added Pd / C (20 mg). The reaction mixture was stirred overnight at room temperature under a hydrogen atmosphere, then filtered through celite to remove Pd / C, and the filtrate was concentrated by distillation under reduced pressure to give a colorless oily product (120 mg, yield 89.5%).

[0892] ESI-MS m / z calcd for [C 14 H 23 N3][M+H] + : 234.2; found: 234.4 2.6

[0894] (R)-2-(4-(6,6-Dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02053)

[0895]

[0896] To a solution of (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (60 mg, 0.41 mmol) in DMF (7 mL) was added 6,6-dimethyl-3-(piperidin-4-yl)-4,5,6,7-tetrahydro-1H-indazole (120 mg, 0.51 mmol) and DIEA (131 mg, 1.03 mmol). The mixture was then stirred at 70 °C for 3 h, and after completion of the reaction, the mixture was concentrated by distillation under reduced pressure to remove the solvent. The crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give a white solid product (20.75 mg, yield 8.33%).

[0897] ESI-MS m / z calcd for [C 25 H 36 N6O2S][M+H] + : 485.3; found: 485.0

[0898] 11H NMR (400 MHz, DMSO-d6) δ 11.95–11.82 (m, 1H), 7.38–7.30 (m, 1H), 4.84 (t, J = 5.6 Hz, 1H), 4.81–4.62 (m, 2H), 3.75–3.68 (m, 2H), 3.45–3.36 (m, 1H), 3.24–3.16 (m, 1H), 3.01–2.82 (m, 5H), 2.39–2.27 (m, 6H), 2.19–2.10 (m, 2H), 1.86–1.70 (m, 4H), 1.60–1.48 (m, 2H), 1.43 (t, J = 6.4 Hz, 2H), 0.93 (s, 6H).

[0899]

[0900] 1. Synthetic Scheme:

[0901]

[0902] 2. Experimental Section: 2.1

[0904] 5-(Benzyloxy)-1-(triisopropylsilyl)-1H-indole (02058-1)

[0905]

[0906] At 0 °C, a solution of NaH (60%, 699 mg, 17.48 mmol) in THF (20 mL) was added dropwise to a solution of 5-(benzyloxy)-1H-indole (3 g, 13.45 mmol) in anhydrous THF (20 mL). The mixture was slowly warmed to room temperature within 30 minutes and then, at 0 °C, chlorotriisopropylsilane (3.37 g, 17.48 mmol) was added dropwise within 5 minutes. The reaction solution was slowly warmed to room temperature and stirred for 4 hours. Then, the reaction was quenched with saturated aqueous NH4Cl solution (20 mL) at 0 °C and extracted three times with Et2O (15 mL). The combined organic phases were dried over anhydrous magnesium sulfate and concentrated to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0–10%, silica gel - CS 40 g, 40 mL / min, silica gel, UV 254) to obtain a white solid product (3.2 g, yield 62.69%).

[0907] ESI-MS m / z calcd for [C9H 10 FNO2], NO MS was found 2.2

[0909] 1-(Triisopropylsilyl)-1H-indol-5-ol (02058-2)

[0910]

[0911] At room temperature, Pd / C (120 mg) was added to a solution of 5-(benzyloxy)-1-(triisopropylsilyl)-1H-indole (3.2 g, 8.43 mmol) in EtOH (40 mL). The mixture was stirred overnight under a hydrogen atmosphere, filtered through diatomaceous earth, and the filtrate was distilled under reduced pressure to give a colorless oily product (2.3 g, 94.3%).

[0912] ESI-MS m / z calcd for [C 17 H 27 NOSi][M+H] + : 290.2; found: 290.2 2.3

[0914] tert-Butyl 3-((1H-indol-5-yl)oxy)azetidine-1-carboxylate (02058-3)

[0915]

[0916] To a solution of 1-(triisopropylsilyl)-1H-indol-5-ol (2.67 g, 9.22 mmol) and Cs2CO3 (9.0 g, 27.67 mmol) in DMF (50 mL) was added tert-butyl 3-iodoazetidine-1-carboxylate (3.1 g, 11.07 mmol). The reaction mixture was stirred at 140 °C for 3 hours, and then the mixture was distilled under reduced pressure to remove the solvent. Water (150 mL) was added, and the mixture was extracted twice with EA (75 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 - 50%, silica gel - CS 40 g, 50 mL / min, silica gel, UV 254) to give a yellow solid product (480 mg, yield 81.5%).

[0917] ESI-MS m / z calcd for [C 16 H 20 N2O3][M+H] + : 289.2; found: 289.1 2.4

[0919] (R)-2-(3-((1H-indol-5-yl)oxy)azetidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02058)

[0920]

[0921] tert-Butyl 3-((1H-indol-5-yl)oxy)azetidine-1-carboxylate (50 mg, 0.17 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (49 mg, 0.17 mmol) in a solution of HFP (2 mL) were stirred at 120 °C for 2 h under microwave conditions. After completion of the reaction, the mixture was distilled under reduced pressure to remove the solvent, and the crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give a white solid product (23.54 mg, yield 30.89%).

[0922] ESI-MS m / z calcd for [C 22 H 25 N5O3S][M+H] + : 440.2; found: 440.0

[0923] 1 H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 7.46 (s, 1H), 7.32–7.30 (m, 2H), 6.93 (d, J = 2.4 Hz, 1H), 6.72 (dd, J = 8.8, 2.4 Hz, 1H), 6.35 (t, J = 2.0 Hz, 1H), 5.11–5.06 (m, 1H), 4.85 (t, J = 5.6 Hz, 1H), 4.45 (dd, J = 9.6, 6.4 Hz, 2H), 3.95–3.92 (m, (m, 2H), 2.38–2.25 (m, 2H), 2.14–2.10 (m, 2H), 1.82–1.65 (m, 2H).

[0924]

[0925] 1. Synthetic Scheme:

[0926]

[0927] 2. Experimental Section: 2.1

[0929] tert-Butyl 4-(5-chloropyrimidin-2-yl)piperidine-1-carboxylate (A-3)

[0930]

[0931] To a solution of 4-cyanopiperidine hydrochloride (3.1 g, 21.2 mmol) in 4N HCl / 1,4-dioxane (10.6 mL, 42.4 mmol) was added MeOH (2.57 mL, 63.6 mmol) while maintaining the temperature below 10 °C. The mixture was cooled to 5 °C, and a solution of 25% NaOMe in MeOH (13.74 g, 63.6 mmol) was added while maintaining the temperature below 15 °C. 7N NH3 / MeOH (4.54 mL, 31.8 mmol) was added to the above mixture, and the mixture was stirred at room temperature for 2 hours. Then the mixture was concentrated under reduced pressure at 60 °C to obtain a 1,4-dioxane solution of the crude product (this solution was not separated).

[0932] The 1,4-dioxane solution of the above intermediate compound was cooled to 0 °C, and a solution of 25% NaOMe in MeOH (11.45 g, 53.0 mmol) was added. Then the mixture was stirred for 30 minutes, and the compound (Z)-N-(2-chloro-3-(dimethylamino)allylidene)-N-methylmethanaminium hexafluorophosphate (5.52 g, 18.02 mmol) was added to the above mixture in two portions within 10 minutes at room temperature, and the mixture was stirred at room temperature for 6 hours. The mixture was concentrated by distillation under reduced pressure, the crude product was dispersed in DCM (100 mL), TEA (10 mL, 71.8 mmol) and (Boc)2O (9.24 g, 42.4 mmol) were added, then the mixture was stirred at room temperature for 3 hours, water (100 mL) was added, and the mixture was extracted twice with DCM (150 mL). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 - 1 / 3, silica gel - CS 80 g, 50 mL / min, silica gel, UV 254) to obtain a yellow oily product (2.50 g, yield 39.7%).

[0933] ESI-MS m / z calcd for[C 14 H 20 ClN3O2][M - 56 + H] + : 298.1; found: 242.3 2.2

[0935] 5-chloro-2-(piperidin-4-yl)pyrimidine (A-4)

[0936]

[0937] To a solution of tert-butyl 4-(5-chloropyrimidin-2-yl)piperidine-1-carboxylate (100 mg, 0.335 mmol) in DCM (5.0 mL) was added TFA (0.5 mL). The mixture was stirred overnight at room temperature, and the pH of the solution was adjusted to 8 with TEA. The solvent was concentrated under reduced pressure to give the crude product as a yellow oil (135 mg, yield 100%) directly for the next step.

[0938] ESI-MS m / z calcd for[C9H 12 ClN3][M+H] + :198.1; found:198.3 2.3

[0940] tert-Butyl 2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (02060-1)

[0941]

[0942] To a solution of tert-butyl 2,4-dichloro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (345 mg, 1.19 mmol) in MeCN (10 mL) and TEA (3 mL) was added (1-aminocyclobutyl)methanol (120 mg, 1.19 mmol). The mixture was then stirred at 70 °C for 16 h. The mixture was distilled under reduced pressure to remove the solvent, water (20 mL) was added, and the mixture was extracted three times with DCM (20 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 to 1 / 0, silica gel - CS20 g, 40 mL / min, UV 254) to give the product as a yellow solid (150.0 mg, yield 35.6%).

[0943] ESI-MS m / z calcd for[C 16 H 23 ClN4O3][M+H] + :355.1; found:355.2 2.4

[0945] tert-Butyl 2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (02060-2)

[0946]

[0947] To a solution of tert-butyl 2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (60 mg, 0.17 mmol) in DMF (4 mL) and DIEA (1 mL) was added 5-chloro-2-(piperidin-4-yl)pyrimidine (135 mg, 0.335 mmol). The mixture was then stirred at 120 °C overnight. The reaction mixture was concentrated under reduced pressure, and the crude product was purified by column chromatography (EA / PE = 0 / 1 to 1 / 0, silica gel - CS20 g, 40 mL / min, silica gel, UV 254), to give the yellow solid product (40.0 mg, yield 45.6%).

[0948] ESI-MS m / z calcd for[C 25 H 34 ClN7O3][M+H] + : 516.2; found: 516.0 2.5

[0950] (1-((2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)amino)cyclobutyl)methanol (MX02060)

[0951]

[0952] To a solution of tert-butyl 2-(4-(5-chloropyrimidin-2-yl)piperidin-1-yl)-4-[(1-(hydroxymethyl)cyclobutyl)amino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (40 mg, 0.078 mmol) in DCM (3 mL) was added TFA (0.3 mL), and the mixture was then stirred at room temperature overnight. The pH of the reaction solution was adjusted to 7 with 1N aqueous NaHCO3. The solvent was removed by distillation under reduced pressure, and the crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10μm 19*250mm, 20 mL / min, UV 254], to give the white solid product (19.05 mg, yield 59.0%).

[0953] ESI-MS m / z calcd for[C 20 H 26 ClN7O][M+H] + : 416.2; found: 416.0

[0954] 11H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 2H), 6.47 (s, 1H), 4.79 (t, J = 5.6 Hz, 1H), 4.61 (d, J = 12.8 Hz, 2H), 4.27–4.21 (m, 1H), 3.80–3.67 (m, 6H), 3.15–3.09 (m, 1H), 2.95–2.89 (m, 2H), 2.25–2.11 (m, 4H), 1.89–1.86 (m, 2H), 1.80–1.73 (m, 2H), 1.67–1.57 (m, 2H).

[0955]

[0956] 1. Synthetic Scheme:

[0957]

[0958] 2. Experimental Section: 2.1

[0960] (1-(5-Chloropyrimidin-2-yl)piperidin-4-yl)carbamic acid tert-butyl ester (02063-1)

[0961]

[0962] At room temperature, cesium carbonate (1.97 g, 6.04 mmol) and 2,5-dichloropyrimidine (450 mg, 3.02 mmol) were added to a solution of tert-butyl piperidin-4-ylcarbamate (664 mg, 3.32 mmol) in 1,4-dioxane (8 mL). The mixture was stirred at 100 °C for 3 h, water (30 mL) was added, and the mixture was extracted three times with EA (30 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0–50%, Silica-CS 20 g, 20 mL / min, silica gel, UV 254) to give a yellow solid product (800 mg, yield 84.6%).

[0963] ESI-MS m / z calcd for [C 14 H 21 ClN4O2][M+H] + : 313.1; found: 313.2 2.2

[0965] 1-(5-Chloropyrimidin-2-yl)piperidin-4-amine (02063-2)

[0966]

[0967] To a solution of tert-butyl (1-(5-chloropyrimidin-2-yl)piperidin-4-yl)carbamate (210 mg, 0.67 mmol) in DCM (5 mL) was added TFA (0.5 mL). The reaction mixture was stirred overnight at room temperature, and the solvent was concentrated by distillation under reduced pressure to obtain a crude yellow oil (230 mg, yield 100%) which was directly used in the next step.

[0968] ESI-MS m / z calcd for[C9H 13 ClN4][M+H] + :213.1; found:213.2 2.3

[0970] (R)-2-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)amino)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02063)

[0971]

[0972] To a solution of 1-(5-chloropyrimidin-2-yl)piperidin-4-amine (230 mg, 0.67 mmol) in DMF (5 mL) and DIEA (1 mL) was added (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (100 mg, 0.347 mmol). The reaction mixture was stirred at 80 °C for 16 h, the mixture was concentrated by distillation under reduced pressure, and the crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to obtain a white solid product (12 mg, yield 7.5%).

[0973] ESI-MS m / z calcd for[C 20 H 26 ClN7O2S][M+H] + : 464.2; found:464.0

[0974] 11H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 2H), 7.31–7.24 (m, 2H), 4.87 (t, J = 5.6 Hz, 1H), 4.49 (d, J = 13.2 Hz, 2H), 3.94–3.90 (m, 1H), 3.72 (d, J = 5.2 Hz, 2H), 3.39–3.31 (m, 1H), 3.22–3.04 (m, 3H), 2.88–2.81 (m, 2H), 2.41–2.30 (m, 2H), 2.17–2.12 (m, 2H), 1.88–1.71 (m, 4H), 1.44–1.36 (m, 2H).

[0975]

[0976] 1. Synthesis Scheme:

[0977]

[0978] 2. Experimental Section: 2.1

[0980] 1-Benzyl-N-((1R,2R)-2-hydroxycyclohexyl)piperidine-4-carboxamide (02069-1)

[0981]

[0982] To a solution of 1-benzylpiperidine-4-carboxylic acid (512 mg, 2.34 mmol) in DCM (8 mL) was added (COCl)2 (358 mg, 2.82 mmol). The mixture was stirred at room temperature for 1 hour under nitrogen protection. The solvent was removed by distillation under reduced pressure. The resulting crude product was added to DCM (8 mL), (1R,2R)-2-aminocyclohexanol (270 mg, 2.34 mmol), and TEA (709 mg, 7.02 mmol). Then the mixture was stirred at room temperature overnight. After the reaction was complete, water (50 mL) was added, and the mixture was extracted three times with EA (50 mL). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a white solid product (602 mg, yield 81%).

[0983] ESI-MS m / z calcd for [C 19 H 28 N2O2][M + H] + : 317.2; found: 317.3 The

[0985] (R)-1-Benzyl-N-(2-oxocyclohexyl)piperidine-4-carboxamide (02069-2)

[0986]

[0987] To a solution of 1-benzyl-N-((1R,2R)-2-hydroxycyclohexyl)piperidine-4-carboxamide (602 mg, 1.90 mmol) in DCM (15 mL) was added PCC (1.23 g, 5.71 mmol). The resulting reaction mixture was stirred at room temperature overnight. The mixture was distilled under reduced pressure to remove the solvent, water (15 mL) was added, and the mixture was extracted three times with EA (50 mL). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give a white solid product (340 mg, yield 56%).

[0988] ESI-MS m / z calcd for[C 19 H 26 N2O2][M+H] + : 315.2; found: 315.2 2.3

[0990] 2-(1-benzylpiperidin-4-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazole (02069-3)

[0991]

[0992] To a solution of (R)-1-benzyl-N-(2-oxocyclohexyl)piperidine-4-carboxamide (140 mg, 0.44 mmol) in HOAc (5 mL) was added CH3COONH4 (338 mg, 4.4 mmol). The mixture was stirred at 150 °C under nitrogen for 20 minutes. After consumption of the starting material, the reaction mixture was concentrated. The crude product was purified by reverse-phase column chromatography (MeCN / H₂O = 1 / 20 - 1 / 1, C-18 column, 20 mL / min, UV 254) to give a yellow solid product (72 mg, yield 55%).

[0993] ESI-MS m / z calcd for[C 19 H 25 N3][M+H] + : 296.2; found: 296.2 2.4

[0995] 2-(piperidin-4-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazole (02069-4)

[0996]

[0997] To a solution of 2-(1-benzylpiperidin-4-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazole (72 mg, 0.24 mmol) in MeOH (3 mL) was added Pd / C (24 mg). The mixture was stirred overnight at room temperature under a hydrogen atmosphere. After the starting material was consumed, the mixture was filtered and the filtrate was concentrated to give a colorless oil (40 mg, 80% yield).

[0998] ESI-MS m / z calcd for[C 12 H 19 N3][M+H] + : 206.2; found: 206.4 2.5

[1000] (R)-4-((1-(hydroxymethyl)cyclobutyl)amino)-2-(4-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02069)

[1001]

[1002] To a solution of 2-(piperidin-4-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazole (40 mg, 0.20 mmol) in 1,4-dioxane (4 mL) were added (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (57 mg, 0.20 mmol) and DIEA (77 mg, 0. 60 mmol). The mixture was stirred for 2 hours at 110 °C under a nitrogen atmosphere. After the starting materials were consumed, the reaction mixture was concentrated. The crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give a white solid product (8.55 mg, 9% yield).

[1003] ESI-MS m / z calcd for[C 23 H 32 N6O2S][M+H] + : 457.2; found: 457.0

[1004] 11H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 7.37 (s, 1H), 4.86 (t, J = 5.6 Hz, 1H), 4.62 (d, J = 11.6 Hz, 2H), 3.72–3.69 (m, 2H), 3.45–3.36 (m, 1H), 3.23–3.16 (m, 1H), 3.03–2.83 (m, 5H), 2.41–2.26 (m, 6H), 2.19–2.13 (m, 2H), 1.85–1.73 (m, 4H), 1.68–1.66 (m, 4H), 1.58–1.54 (m, 2H),.

[1005]

[1006] 1. Synthesis Scheme:

[1007]

[1008] 2. Experimental Section: 2.1

[1010] Methyl 2-(4-(((2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetate (02075-1)

[1011]

[1012] At room temperature, methyl 2-(4-aminophenyl)acetate (2.39 g, 14.48 mmol) was added to a solution of 2,4-dichloro-6,7-dihydrothieno[3,2-d]pyrimidine (3 g, 14.48 mmol) and DIEA (5.61 g, 43.44 mmol) in DMF (50 mL). The mixture was stirred at 100 °C overnight, then water (50 mL) was added to the reaction mixture, and it was extracted twice with DCM (70 mL). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (EA / PE = 0 / 1 - 1 / 2, silica gel - CS 80 g, 50 mL / min, UV 254) to obtain an orange solid product (3.11 g, yield 63.9%).

[1013] ESI-MS m / z calcd for [C 15 H 14 ClN3O2S][M + H] + : 336.1; found: 336.0

[1014] 2.2 Methyl (R)-2-(4-((2-chloro-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetate (02075-2)

[1015]

[1016] To a solution of methyl 2-(4-((2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)-2-fluorophenyl)acetate (420 mg, 1.25 mmol) and S-1,1'-bi-2-naphthol (37.2 mg, 0.13 mmol) in DCM (10 mL) were added titanium(IV) isopropoxide (17.8 mg, 0.06 mmol) and water (22.5 mg, 1.25 mmol). After the mixture was stirred at room temperature for 16 h under nitrogen protection, 70% aqueous tert-butyl hydroperoxide (123.9 mg, 1.37 mmol) was added in one portion, and then the mixture was stirred at room temperature for 2 h. Water (20 mL) was added, and the mixture was extracted three times with DCM (60 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (DCM / MeOH = 1 / 0 - 20 / 1, silica gel - CS 40 g, 50 mL / min, silica gel, UV 254) to give a white solid product (367 mg, yield 83.4%).

[1017] ESI-MS m / z calcd for [C 15 H 14 ClN3O3S][M + H]+: 352.0; found: 352.0 2.3

[1019] (R)-2-(4-((2-(4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetate (02075-3)

[1020]

[1021] To a solution of methyl (R)-2-(4-((2-chloro-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetate (30 mg, 0.08 mmol) and DIEA (31 mg, 0.24 mmol) in DMF (5 mL) was added 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (9.8 mg, 0.08 mmol). The mixture was then stirred at 90 °C for 1 h. After consumption of the starting material, the reaction mixture was concentrated. The crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the product as a white solid (27 mg, yield 72.2%).

[1022] ESI-MS m / z calcd for [C 21 H 22 FN6O3S][M+H] + : 439.2; found: 439.0 2.4

[1024] (R)-2-(4-((2-(4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetic acid (MX02075)

[1025]

[1026] To a solution of methyl (R)-2-(4-((2-(4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)phenyl)acetate (27 mg, 0.06 mmol) in EtOH (3 mL) was added 1N aqueous LiOH solution (0.6 mL, 0.6 mmol). The mixture was then stirred at 50 °C for 1 h. The pH of the reaction solution was adjusted to 6 with 1N aqueous HCl solution. The solvent was removed by distillation under reduced pressure. The crude product was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the product as a white solid (11.57 mg, yield 35.1%).

[1027] ESI-MS m / z calcd for [C 20 H 20 N6O3S][M+H] +: 425.1; found: 425.0

[1028] 1 1H NMR (400 MHz, DMSO-d6 + D2O) δ 7.61 (d, J = 8.0 Hz, 2H), 7.47 (s, 1H), 7.28 (d, J = 8.8 Hz, 2H), 4.89–4.87 (m, 2H), 4.02–4.00 (m, 2H), 3.59–3.54 (m, 3H), 3.35–3.32 (m, 1H), 3.14–3.02 (m, 2H), 2.65–2.63 (m, 2H).

[1029]

[1030] 1. Synthetic Scheme:

[1031]

[1032] 2. Experimental Section: 2.1

[1034] tert-Butyl 4-(5-chloropyrimidin-2-yl)-1,4-diazepane-1-carboxylate (02077-1)

[1035]

[1036] A mixture of 2,5-dichloropyrimidine (500 mg, 3.36 mmol), tert-butyl 1,4-diazepane-1-carboxylate (673 mg, 3.36 mmol) and DIEA (2.8 mL, 16.8 mmol) in DMF (20 mL) was stirred overnight under argon at 80 °C. After cooling, the reaction mixture was evaporated under reduced pressure to remove the solvent. The crude product was purified by column chromatography (EA / PE = 0–1 / 9, silica gel - CS 40 g, 40 mL / min, UV 254), and a white solid product (981 mg, yield 93.4%) was obtained.

[1037] ESI-MS m / z calcd for [C 14 H 21 ClN4O2][M + H] + : 313.1; found: 313.2 2.2

[1039] 1-(5-Chloropyrimidin-2-yl)-1,4-diazepane (02077-2)

[1040]

[1041] To a solution of tert-butyl 4-(5-chloropyrimidin-2-yl)-1,4-diazepane-1-carboxylate (200 mg, 0.64 mmol) in DCM (20 mL) was added TFA (4 mL). The mixture was stirred at 35 °C under argon for 2 h, and then the reaction mixture was concentrated to dryness to give a crude product as a pale yellow oil (136 mg, yield 99.9%).

[1042] ESI-MS m / z calcd for[C9H 13 ClN4][M+H] + :213.1;found:213.2 2.3

[1044] (R)-2-(4-(5-Chloropyrimidin-2-yl)-1,4-diazepan-1-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02077)

[1045]

[1046] To a solution of 1-(5-chloropyrimidin-2-yl)-1,4-diazepane (68 mg, 0.32 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (92 mg, 0.32 mmol) in DMF (20 mL) was added DIEA (0.26 mL, 1.6 mmol). The mixture was stirred at 80 °C under argon overnight, and then the mixture was distilled under reduced pressure to remove the solvent. The crude product was purified by column chromatography (MeOH / DCM = 0 - 1 / 9, silica gel - CS20 g, 20 mL / min, UV 254) to give a crude product (90 mg), and then the crude product was further purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give a white solid product (73.60 mg, yield 49.6%).

[1047] ESI-MS m / z calcd for[C 20 H 26 ClN7O2S][M+H] + :464.2;found:463.9

[1048] 11H NMR (400 MHz, DMSO-d6) δ 8.40–8.38 (m, 2H), 7.30 (s, 1H), 4.85 (t, J = 5.6 Hz, 1H), 3.95–3.78 (m, 4H), 3.74–3.57 (m, 6H), 3.42–3.36 (m, 1H), 3.23–3.15 (m, 1H), 2.94–2.81 (m, 2H), 2.36–2.28 (m, 2H), 2.16–2.14 (m, 2H), 1.86–1.72 (m, 4H).

[1049]

[1050] 1. Synthetic Scheme:

[1051]

[1052] 2. Experimental Section: 2.1

[1054] tert-Butyl 3-ethoxy-2,5,6,7-tetrahydro-1H-1,4-diazepine-1-carboxylate (02078-1)

[1055]

[1056] To a solution of tert-butyl 3-oxo-1,4-diazepane-1-carboxylate (500 mg, 2.34 mmol) in DCM (10 mL) was added triethyloxonium tetrafluoroborate (613 mg, 3.50 mmol). The mixture was stirred overnight at room temperature under nitrogen protection. After the starting material was consumed, the reaction mixture was quenched with saturated aqueous NaHCO3 (50 mL) and extracted three times with EA (50 mL). The combined organic layers were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction and concentrated to give a yellow oily product (525 mg, yield 93%).

[1057] ESI-MS m / z calcd for [C 12 H 22 N2O3][M + H] + : 243.2; found: 243.3 2.2

[1059] tert-Butyl 3-(2-(methoxycarbonyl)hydrazino)-2,5,6,7-tetrahydro-1H-1,4-diazepine-1-carboxylate (02078-2)

[1060]

[1061] To a solution of tert-butyl 3-ethoxy-2,5,6,7-tetrahydro-1H-1,4-diazepine-1-carboxylate (525 mg, 2.17 mmol) in MeOH (5 mL) was added methyl hydrazinecarboxylate (195 mg, 2.17 mmol). The mixture was stirred at room temperature for 16 h under nitrogen protection. After the starting material was consumed, the reaction mixture was concentrated. The resulting crude product was purified by column chromatography (MeCN / H2O = 1 / 20 - 1 / 1, C-18 column, 30 mL / min, UV 254) to give a colorless oil (126 mg, yield 20%).

[1062] ESI-MS m / z calcd for[C 12 H 22 N4O4][M+H] + :287.2; found:287.1 2.3

[1064] tert-butyl 3-oxo-5,6,7,9-tetrahydro-2H-[1,2,4]triazolo[4,3-a][1,4]diazepine-8(3H)-carboxylate (02078-3)

[1065]

[1066] To a solution of tert-butyl 3-(2-(methoxycarbonyl)hydrazino)-2,5,6,7-tetrahydro-1H-1,4-diazepine-1-carboxylate (126 mg, 0.44 mmol) in EtOH (3 mL) was added NaOMe (24 mg, 0.44 mmol). The mixture was stirred at 75 °C for 4 h under nitrogen protection. After the starting material was consumed, the reaction mixture was concentrated. The resulting crude product was purified by reverse-phase column chromatography (MeCN / H2O = 1 / 20 - 1 / 1, C-18 column, 20 mL / min, UV 254) to give a white solid (61 mg, yield 55%).

[1067] ESI-MS m / z calcd for[C 11 H 18 N4O3][M+H] + :255.1; found:255.2 2.4

[1069] 6,7,8,9-tetrahydro-2H-[1,2,4]triazolo[4,3-a][1,4]diazepin-3(5H)-one (02078-4)

[1070]

[1071] To a solution of tert-butyl 3-oxo-5,6,7,9-tetrahydro-2H-[1,2,4]triazolo[4,3-a][1,4]diazepine-8(3H)-carboxylate (61 mg, 0.24 mmol) in DCM (2 mL) was added TFA (0.2 mL). The mixture was stirred at room temperature under nitrogen for 3 hours. After consumption of the starting material, the mixture was concentrated to give the product as a colorless oil (33 mg, 89% yield).

[1072] ESI-MS m / z calcd for[C 12 H 22 N4O4][M+H] + : 155.1; found: 155.3 2.5

[1074] (R)-8-(4-((1-(Hydroxymethyl)cyclobutyl)amino)-5-oxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)-6,7,8,9-tetrahydro-2H-[1,2,4]triazolo[4,3-a][1,4]diazepin-3(5H)-one (MX02078)

[1075]

[1076] To a solution of 6,7,8,9-tetrahydro-2H-[1,2,4]triazolo[4,3-a][1,4]diazepin-3(5H)-one (33 mg, 0.21 mmol) in DMF (3 mL) was added (R)-2-chloro-4-[(1-(hydroxymethyl)cyclobutyl)amino]-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (60 mg, 0.21 mmol) and DIEA (81 mg, 0.63 mmol). The mixture was stirred at 100 °C under nitrogen for 2 hours. After consumption of the starting material, the reaction mixture was concentrated. The crude product obtained was purified by preparative HPLC [MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254] to give the product as a white solid (7.13 mg, yield of 8%).

[1077] ESI-MS m / z calcd for[C 17 H 23 N7O3S][M+H] + : 406.2; found: 406.2

[1078] 11H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 7.52–7.38 (m, 1H), 4.83–4.72 (m, 3H), 4.04–3.94 (m, 2H), 3.80–3.70 (m, 4H), 3.44–3.36 (m, 1H), 3.23–3.16 (m, 1H), 2.95–2.83 (m, 2H), 2.37–2.14 (m, 4H), 1.77–1.71 (m, 4H).

[1079]

[1080] 1. Synthetic Scheme:

[1081]

[1082] 2. Experimental Section: 2.1

[1084] (R)-2-(2-Chloro-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (MX02089)

[1085]

[1086] tert-Butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (40 mg, 0.148 mmol) and (R)-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2-d]pyrimidine 5-oxide (40 mg, 0.138 mmol) in a solution of HFP (3 mL) were stirred at 120 °C for 2 h under microwave conditions. After completion of the reaction, water (10 mL) was added to the reaction mixture, and the mixture was extracted twice with DCM (10 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative HPLC (MeCN / H2O (10 mmol / L NH4HCO3), X-Select 10 μm 19*250 mm, 20 mL / min, UV 254) to give the white solid product (16.6 mg, yield 19.1%).

[1087] ESI-MS m / z calcd for [C 19 H 22 ClN5O2S][M + H] + : 420.12; found: 420.0

[1088] 11H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 8.4 Hz, 1H), 7.52 (s, 1H), 7.35 (d, J = 8.4 Hz, 1H), 4.90–4.86 (m, 3H), 4.06–4.04 (m, 2H), 3.75–3.74 (m, 2H), 3.43–3.39 (m, 1H), 3.22–3.19 (m, 1H), 2.99–2.94 (m, 1H), 2.90–2.86 (m, 3H), 2.42–2.29 (m, 2H), 2.21–2.19 (m, 2H), 1.80–1.78 (m, 2H).

[1089]

[1090] 1. Synthetic Scheme:

[1091]

[1092] 2. Experimental Section: 2.1

[1094] tert-Butyl 2-cyano-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (02090-1)

[1095] <W

[1096] To a solution of tert-butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (230 mg, 0.86 mmol) in DMF (15 mL) were added Zn powder (562.4 mg, 8.6 mmol), Zn(CN)2 (1.01 g, 8.6 mmol), Pd2(dba)3 (238.1 mg, 0.26 mmol) and dppf (144.1 mg, 0.26 mmol). The reaction mixture was then heated to 120 °C and stirred for 6 h, cooled to room temperature and concentrated. Water (10 mL) was added, and the mixture was extracted twice with DCM (10 mL). The combined organic layers were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (EA...

Claims

1. A compound represented by the following formula H, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug: Wherein: X1 represents a chemical bond, C 1-20 an alkylene group, O, S, NR q , S(=O), S(=O)2 or C(=O); R q selected from H, halogen, OH, CN, NO2, oxo(=O), thio(=S), unsubstituted or optionally substituted by 1, 2 or more R f substituted groups as follows: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 、-C(O)OR 42 、-OC(O)R 43 、-S(O)2R 44 、-S(O)2OR 45 、-OS(O)2R 46 、-P(O)(OR 47 )(OR 48 ); L represents a chemical bond, C 2-20 an alkynyl group or Cy; wherein, L can be connected to X1 or R c at any position; Cy represents a 3- to 20-membered heterocyclic group, C 6-20 aryl, or a 5- to 20-membered heteroaryl, wherein the 3- to 20-membered heterocyclic group, C 6-20 aryl, or 5- to 20-membered heteroaryl may optionally be fused to a 4- to 7-membered cycloalkyl group, provided that when the heterocyclic group contains an N atom, the heterocyclic group may be bonded to the carbon atom at the 2-position of the pyrimidine ring in formula H through its N atom or C atom; W represents a chemical bond, CH, O, S, N, -S(O)-, -S(O)2-, -C(O), sub-C 1-6 alkyl, sub-C 2-6 alkenyl or sub-C 2-6 alkynyl; R2 is selected from absent, H, unsubstituted or optionally substituted by one, two or more Rs d1 substituted with the following groups: C 6-20 aryl, 5- to 20-membered heteroaryl; R 2’ represents absent, H, halogen, OH, CN, unsubstituted or optionally substituted by 1, 2 or more R d2 substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5 - 20 membered heteroaryl, 3 - 20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5 - 20 membered heteroaryloxy, 3 - 20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5 - 20 membered heteroarylthio, 3 - 20 membered heterocyclic thio group, NH2; provided that R2 and R 2’ are not simultaneously "absent"; Alternatively, R2, R 2’ together with the atoms to which it may be attached, may form an unsubstituted or optionally substituted by 1, 2 or more R d3 substituted with the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, 6-20 membered aryl; R a represents H or -X-R3; X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R3 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d4 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; R b represents H or -Y-R4; Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d5 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; The condition is R a and R b are not both H at the same time; Alternatively, R a , R b together with the atom to which it is attached forms an unsubstituted or optionally substituted by 1, 2 or more R d6 substituted with the following groups: C 5-20 cycloalkenyl, 3- to 20-membered heterocyclic group, 5- to 20-membered heteroaryl, 6- to 20-membered aryl; Each R d1 、R d2 、R d3 、R d4 、R d5 、R d6 is the same as or different from each other and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), SO, SO2, and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 31 、-CH2-C(O)R 31 、-C(O)OR 32 、-CH2C(O)OR 32 、-C(O)NHR 32 、-CH2C(O)NHR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 ); Alternatively, when there are more than two substituents selected from R d1 , R d2 , R d3 , R d4 , R d5 , R d6 on the same group, the two substituents may together with the atoms to which they are attached form the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e : C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R c is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl-O-C 6-20 aryl-, 5-20 membered heteroaryl-N-C 6-20 aryl-, 5-20 membered heteroaryl-S-C 6-20 aryl-, 5-20 membered heteroaryl-CH2-C 6-20 aryl-, C 4-10 cycloalkyl-fused C 6-20 aryl-, 4-10 membered heterocycloalkyl-fused C 6-20 aryl-, 4-10 membered heterocycloalkenyl-fused C 6-20 aryl-, C 4-10 cycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkenyl-C 6-20 aryl-, 5-20 membered heteroaryl, C 4-10 cycloalkyl-fused 5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-fused 5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-fused 5-20 membered heteroaryl-, C 4-10 cycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryl-, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 Arylthio, 5- to 20-membered heteroarylthio, 3- to 20-membered heterocyclicthio, NH2, -C(O)R 31 , -C(O)OR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 ); m is an integer selected from 1 to 10; Each R e is the same or different and is independently selected from H, halogen, OH, CN, NO2, NH2, oxo(=O), thioxo(=S), O-CONH2, O-CONHR f , and the following groups which are unsubstituted or optionally substituted by one, two or more R f : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, C 1-8 -heteroalkyl-condensed-C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 , -C(O)OR 42 , -OC(O)R 43 , -S(O)2R 44 , -S(O)2OR 45 , -OS(O)2R 46 , -P(O)(OR 47 )(OR 48 ); Alternatively, when there are two or more substituents selected from R e on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f of the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R f is the same as or different from one another, and is independently selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R g groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 51 , -C(O)OR 52 , -OC(O)R 53 , -S(O)2R 54 , -S(O)2OR 55 , -OS(O)2R 56 , -P(O)(OR 57 )(OR 58 ); Alternatively, when there are more than two substituents selected from R f on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R g substituted group selected from the following: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R g is the same or different and is independently selected from the group consisting of H, halogen, OH, CN, NO2, oxo (═O), thioxo (═S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2; Each R 31 、R 32 、R 33 、R 34 、R 35 、R 36 、R 37 、R 38 、R 41 、R 42 、R 43 、R 44 、R 45 、R 46 、R 47 、R 48 、R 51 、R 52 、R 53 、R 54 、R 55 、R 56 、R 57 、R 58 are the same or different and are each independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2; The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, bridged ring, spiro ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, such as 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the state of nitrogen oxide, -S(O)- or -S(O)2-; The said C 6-20 Aryl represents a monocyclic, bicyclic (such as fused ring, bridged ring, spiro ring) or tricyclic hydrocarbon ring that is monovalent, aromatic or partially aromatic and has 6 to 20 carbon atoms, which may be a monoaromatic ring or a polyaromatic ring fused together; The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, bridged ring, spiro ring) or tricyclic aromatic ring system, and the aromatic ring system has 5 to 20 ring atoms and contains 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S. For example, a compound represented by the following formula G, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug: Wherein: Cy represents a chemical bond, a 3- to 20-membered heterocyclic group, a C 6-20 aryl, a 5- to 20-membered heteroaryl, provided that when the heterocyclic group contains an N atom, the heterocyclic group can be bonded to the carbon atom at the 2-position of the pyrimidine ring in formula G through its N atom or C atom; W represents a chemical bond, CH, O, S, N, -S(O)-, -S(O)2-, -C(O), sub-C 1-6 alkyl, sub-C 2-6 alkenyl or sub-C 2-6 alkynyl; R2 is selected from absent, H, unsubstituted or optionally substituted by one, two or more Rs d1 substituted with the following groups: C 6-20 aryl, 5- to 20-membered heteroaryl; R 2’ represents absent, H, halogen, OH, CN, unsubstituted or optionally substituted by 1, 2 or more R d2 substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2; wherein R2 and R 2’ are not both "absent"; Alternatively, R2, R 2’ together with the atoms to which it is attached may form an unsubstituted or optionally substituted by 1, 2 or more R d3 substituted with the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, 6-20 membered aryl; R a represents H or -X-R3; X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R3 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d4 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; R b represents H or -Y-R4; Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d5 with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; wherein R a and R b are not both H; Alternatively, R a , R b together with the atom to which it is attached form an unsubstituted or optionally substituted by 1, 2 or more R d6 substituted with the following groups: C 5-20 cycloalkenyl, 3- to 20-membered heterocyclic group, 5- to 20-membered heteroaryl, 6- to 20-membered aryl; Each R d1 、R d2 、R d3 、R d4 、R d5 、R d6 is the same as or different from each other and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 31 、-CH2-C(O)R 31 、-C(O)OR 32 、-CH2C(O)OR 32 、-C(O)NHR 32 、-CH2C(O)NHR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 ); Alternatively, when there are more than two substituents selected from R d1 , R d2 , R d3 , R d4 , R d5 , R d6 on the same group, the two substituents may together with the atoms to which they are attached form the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e : C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R c is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R e substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 31 、-C(O)OR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 ); m is an integer selected from 1 to 10; Each R e is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R f substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 41 、-C(O)OR 42 、-OC(O)R 43 、-S(O)2R 44 、-S(O)2OR 45 、-OS(O)2R 46 、-P(O)(OR 47 )(OR 48 ); Alternatively, when there are two or more substituents selected from R e on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f of the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R f is the same or different and independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R g of the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 51 , -C(O)OR 52 , -OC(O)R 53 , -S(O)2R 54 , -S(O)2OR 55 , -OS(O)2R 56 , -P(O)(OR 57 )(OR 58 ); Alternatively, when there are more than two substituents selected from R f on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R g substituted following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R g is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2; Each R 31 、R 32 、R 33 、R 34 、R 35 、R 36 、R 37 、R 38 、R 41 、R 42 、R 43 、R 44 、R 45 、R 46 、R 47 、R 48 、R 51 、R 52 、R 53 、R 54 、R 55 、R 56 、R 57 、R 58 are the same or different and are each independently selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2; The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, bridged ring, spiro ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, such as 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the state of nitrogen oxide, -S(O)- or -S(O)2-; Said C 6-20 Aryl represents a monocyclic, bicyclic (such as a fused ring, bridged ring, spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms and being monovalent, aromatic or partially aromatic, which may be a monoaromatic ring or a polyaromatic ring fused together; The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, bridged ring, spiro ring) or tricyclic aromatic ring system, and the aromatic ring system has 5 to 20 ring atoms and contains 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S; Preferably, the cycloalkyl can be saturated or partially saturated; Preferably, the compound does not include a compound selected from the following and / or its stereoisomer and / or its racemate:

2. The compound of formula G, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug according to claim 1, wherein the compound of formula G is selected from the compounds represented by the following formula I, II, III, IV, V, VI, VII or VIII:

3. The compound, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug according to claim 2, wherein the compound of formula I has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)₂ or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and the substituents of each of said substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 ; Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl substituents, R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 or R2 represents hydrogen, a mono- or polycyclic C 6-20- aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 as defined herein. Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 or R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; the groups may each optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atom(s) to which it is attached form a 4-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta position by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; R3 represents H, C 1-6 -alkyl, F, chlorine, bromine, hydroxyl, -CN, -CH2CN, -CH2COOR, -COOR, -CO-NH(CH3)C 1-3 -fluoroalkyl, (C 1-6 -alkyl)-OH, (C 1-6 -alkyl)-OCH3, (C 1-6 -alkyl)-NH2, (C 1-6 -alkyl)-N(C 1-3 -alkyl) or (C 1-6 -alkyl)-NH; R 3’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by one, two or more groups selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R3 and R 3’ together represent oxo, methylene, ethylene, and propylene, which may optionally be substituted with substituents selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 -alkyl); R4 represents H, C 1-6 -alkyl, F, chlorine, bromine, hydroxyl, -CN, -CH2CN, -CH2COOR, -COOR, -CO-NH(CH3)C 1-3 -fluoroalkyl, (C 1-6 -alkyl)-OH, (C 1-6 -alkyl)-OCH3, (C 1-6 -alkyl)-NH2, (C 1-6 -alkyl)-N(C 1-3 -alkyl) or (C 1-6 -alkyl)-NH; R 4’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by one, two or more groups selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R4 and R 4’ together represent oxo, methylene, ethylene, and propylene, which may optionally be substituted with substituents selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3- alkyl); R5 and R6 independently represent H, F, C 1-6 -alkyl, C 1-3 -fluoroalkyl, C 1-6 -alkyl-OH, C 1-6 -alkenyl-OCH3, C 1-6 -alkyl-NH2, C 1-6 -alkynyl-NH(C 1-3 -alkyl) and C 1-6 -alkyl-N(C 1-3 -alkyl)2; Alternatively, R1 and R3, together with the C- and N-atoms of the piperidine, form a saturated or partially saturated 5- or 7-membered heterocyclic group containing two or three nitrogen atoms, which may optionally be substituted by a group selected from -CH3, -CH2CH3, -CH2CH2CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2 and O-(C 1-3- alkyl). Alternatively, R3 and R6 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl); Alternatively, R3 and R5 together form a bridged ring of methylene, ethylene and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2 and O-(C 1-3 alkyl); Alternatively, R3 and R4 together form a bridged ring of methylene, ethylene and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2 and O-(C 1-3 -alkyl); Alternatively, R4 and R6 together form a bridged ring of methylene, ethylene, and propylene, which may optionally be substituted with a group selected from -CH3, -OH, -F, -CF3, -CHF2, -CH2F, -NH2, -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl)2, and O-(C 1-3 alkyl); Alternatively, R4 and R7 together with the carbon atom to which they are attached form a double bond. For example, the examples of R1 can be selected from the following groups: For example, -W-R2R 2’ Examples of may be selected from the following groups:

4. The compound, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug according to claim 2, wherein the compound of formula II has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic C 6-20- aryl), 3-20 membered heterocyclic group-C 6-20- aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 therein, Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 5-10 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ; R2 represents hydrogen, a mono- or polycyclic C 6-20- aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 and the each substituent may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions each by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 substituted by one, two or more of the substituents in; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 5-10 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 or R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-20- aryl, C 6-20- aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused combination or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, R3 represents a group selected from aryl and heteroaryl, each of which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or each is independently optionally substituted by 1, 2 or more substituents selected from 1.1 C 1-3 -alkyl-OR 1.1 SR 1.1 C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 2.3 ; R4 represents a group selected from aryl and heteroaryl, each of which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or each is independently optionally substituted by one, two or more substituents selected from OR 1.1 、C 1-3 -alkyl-OR 1.1 、SR 1.1 、C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 ,C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 ,C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 ,C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by OH, OR 2.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 2.3 substituted by one, two or more of the substituents in; Ring A represents a chemical bond, a mono- or polycyclic C 6-20- aryl group, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 therein, or, Ring A represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and the each substituent may be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 1.2 R 1.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and the groups of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 substituents. For example, examples of the A ring may be selected from the following groups: For example, -W-R2R 2’ Examples of may be selected from the following groups: For example, examples of the -X-R3 substituent may be selected from the following groups:

5. A compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula III has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a single- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and each of said substituents is optionally further substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 as defined herein Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions each by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and the substituents of R 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 and is further optionally substituted by one, two or more substituents selected from OH, OR Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 or R2 represents hydrogen, a mono- or polycyclic C 6-20 aryl, which may optionally be independently substituted at the ortho, para or meta positions each by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted by substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 2.2 R 2.3 as substituents, Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 aryl, C 1-6 -alkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally related heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 2.1 is H or selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C C 6-20 aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 or R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; the groups may each optionally be substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atoms to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic group-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20 aryl and NR 1.2 R 1.3 ; Ring A represents a group selected from heterocycles or heteroaryls, each of which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20 aryl, C 1-6 -alkyl, CC 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and is further optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20 aryl and NR 1.2 R 1.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and the groups may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 and is substituted. For example, examples of the A ring may be selected from the following groups: For example, -W-R2R[[ID=I]] 2’ Examples of may be selected from the following groups:

6. A compound of formula G according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula IV has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); V represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20 aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents, each of said substituents optionally further substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20 aryl and NR 1.2 R 1.3 in Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-20 aryl, C 1-6 , -alkyl, C 6-20 aryl-C 1-6 , 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3 , and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20 aryl and NR 1.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 ; or R2 represents hydrogen, a mono- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and the substituents of each of the substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 as defined above, Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C[[ID=^11]] 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 2.1 or R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the group in each case may optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atom(s) to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta position by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; Ring A represents a chemical bond, a single- or polycyclic C 6-20 aryl group, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 in, or, Ring A represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 , -alkyl alcohol, monocyclic or bicyclic C 3-10 , -cycloalkyl, C 6-10 , -aryl, C 1-6 , -alkyl, C 6-10 , -aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3 and the each substituent may be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl group is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 substituted. For example, examples of the A ring can be selected from the following groups: For example, -W-R2R 2’ Examples of may be selected from the following groups:

7. The compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula V has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); V represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; Or, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and is further optionally substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; wherein R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 or R2 represents hydrogen, a single- or poly-cyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 and the substituents of each of the above substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 among others, Or, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by 1, 2 or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-10 , -aryl, C 1-6 , -alkyl, C 6-10 , -aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 , alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 , aryl), 3-20 membered heterocyclic-C 6-20 , -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 2.1 , and NR 2.2 R 2.3 , and the substituents of R 2.1 , may optionally be further substituted by OH, OR 1-6- , oxo, halogen, CF3, CHF2, CH2F, C 6-10- , alkyl, C 2.2 , aryl and NR 2.3 , R with one, two or more substituents; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; wherein R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents, R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 or R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by 1, 2 or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Or, R2 and R 2’ together form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused combination or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 in, or, Ring A represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-10 , -aryl, C 1-6 , -alkyl, C 6-10 , -aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 , alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 , -aryl), 3-20 membered heterocyclic-C 6-20 , -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3 and the substituents of R 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- , alkyl, C 6-10- , aryl and NR 1.2 R 1.3 in which each substituent may optionally be substituted by one, two or more substituents selected from OH, OR Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl group is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl, R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 . For example, examples of the A ring can be selected from the following groups: For example, -W-R2R 2’ Examples of substituents may be selected from the following groups:

8. The compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled substance, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula VI has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)₂ or C(O), C 1-2 - alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally independently and optionally substituted at the ortho, para or meta positions each by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and is substituted by the substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 in the group, Or, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions each by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 or R2 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each being optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or being substituted by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3- to 20-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 and the each substituent may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The cycloalkyl can be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 ; R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; said group may in each case be optionally substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atom to which it is attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta positions by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; Ring A represents a chemical bond, a single- or polycyclic C 6-20 aryl, which may be independently optionally substituted at the ortho, para or meta positions with one, two, or three groups independently substituted with fluorine, chlorine, bromine, hydroxyl, CN, NH2, or substituted with one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted with one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; or, Ring A represents a group selected from a heterocycle or heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituents, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl group is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocyclic, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20 aryl and COOR 1.1 . For example, examples of the A ring can be selected from the following groups: For example, -W-R2R 2’ Examples of substituents may be selected from the following groups:

9. The compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled substance, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula VII has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)₂ or C(O), C 1-2 -alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 and the substituents of each of said substituents are optionally further substituted by 1, 2 or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH-CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ; R2 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituted by substituents, each of said substituents being optionally further substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 as defined herein Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions with one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or substituted with one, two or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 and is further optionally substituted with one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl group including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The cycloalkyl can be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 or R 2’ represent H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case be optionally substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atom(s) to which they are attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta position by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 20-membered heterocyclic-C 6-20- aryl, 3- to 20-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions by one, two, or three groups independently substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R[[ID=,23]] 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; or, Ring A represents a group selected from heterocycles or heteroaryls, each of which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-10 , -aryl, C 1-6 , -alkyl, C 6-10 , -aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 , -aryl), 3-20 membered heterocyclic-C 6-20 , -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 1.1 and NR 1.2 R 1.3 and is further optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 of the group, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 substituted. For example, examples of the A ring may be selected from the following groups: For example, -W-R2R 2’ Examples of the group may be selected from the following groups:

10. A compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula VIII has the following definitions: Wherein: W represents CH, O, S, N, S(O), S(O)2 or C(O), C 1-2 - alkyl, vinyl or ethynyl; X represents CH2, O, S, NH, S(O), S(O)2 or C(O); Y represents CH2, O, S, NH, S(O), S(O)2 or C(O); Z represents CH2, O, S, NH, S(O), S(O)2 or C(O); R1 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions, each optionally substituted by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituted by substituents, each of which may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions each by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 1.2 and R 1.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 ; R2 represents hydrogen, a mono- or polycyclic C 6-20 -aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, a 3- to 20-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, a 3- to 20-membered heterocycle-C 1-6 -alkyl, a 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, C 1-3 -alkyl-SOR 2.1 , C 1-3 -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 substituents, and each of said substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 2.2 R 2.3 among the substituents, Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by 1, 2 or more substituents selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 and NR 2.2 R 2.3 substituted, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 2.2 R 2.3 ; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl substituents; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the groups of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 ; R 2’ represents H, F, Me, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 6-20 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 6-20 -heterocycle, -NR’R”, fluoro, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, wherein R’ and R” are independently selected from H and C 1-6- alkyl; the groups may each optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, R2 and R 2’ together with the atom to which it is attached form a 4-11 membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta position by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; R4 represents a group selected from aryl and heteroaryl, which is independently optionally substituted at the ortho, para or meta position by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or is independently optionally substituted by 1, 2 or more substituents selected from 1.1 C 1-3 -alkyl-OR 1.1 SR 1.1 C 1-3 -alkyl-SR 1.1 ,SO-R 1.1 C 1-3 -alkyl-SOR 1.1 ,SO2-R 1.1 C 1-3 -alkyl-SO2R 1.1 ,COOR 1.1 ,CH2COOR 1.1 ,CH2CH2COOR 1.1 ,CH=CHCOOR 1.1 ,CO-NR 1.1 CH2CO-NR 1.1 ,CH2CH2CO-NR 1.1 ,CH=CHCO-NR 1.1 ,COR 1.1 ,CH2COR 1.1 C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituents, and each of said substituents may in turn be optionally substituted by OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 substituents; Ring A represents a chemical bond, a mono- or polycyclic C 6-20 -aryl, which may be independently optionally substituted at the ortho, para or meta positions with one, two, or three groups independently substituted with fluorine, chlorine, bromine, hydroxyl, CN, NH2, or substituted with one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(mono- or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-10 aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 of the substituents, and each of said substituents may in turn be optionally substituted with one, two or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl and NR 1.2 R 1.3 ; or, Ring A represents a group selected from heterocycles or heteroaryls, each of which is independently optionally substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-10 -aryl, C 1-6 -alkyl, C 6-10 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20 -aryl), 3-20 membered heterocyclic-C 6-20 -aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and the substituents of NR 1.1 R may each be optionally substituted by one, two or more substituents selected from OH, OR 1-6- , oxo, halogen, CF3, CHF2, CH2F, C 6-10- alkyl, C 1.2 aryl and NR 1.3 R; Heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; Cycloalkyl may be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20 -aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-20 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20 -aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20 aryl; R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20 aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20 aryl, 3-20 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 substituents. For example, examples of the A ring may be selected from the following groups: For example, -W-R2R 2’ Examples of the group may be selected from the following groups: 。 11. A compound according to claim 2, its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug, wherein the compound of formula IX has the following definitions: Wherein: X1 represents a chemical bond, C 1-20 an alkylene group, O, S, NR q , S(=O), S(=O)2 or C(=O); U represents -(CH2) t -, O, S, NR q , S(=O), S(=O)2 or C(=O), where t represents 0, 1, 2 or 3; R q selected from H, halogen, OH, CN, NO2, NH2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R f substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 、-C(O)OR 42 、-OC(O)R 43 、-S(O)2R 44 、-S(O)2OR 45 、-OS(O)2R 46 、-P(O)(OR 47 )(OR 48 ); v represents 0, 1, 2, 3, 4 or 5; L represents a chemical bond, C 2-20 an alkynyl group or Cy; wherein, L can be connected to X1 or R c at any site; Cy represents a chemical bond, a 3- to 20-membered heterocyclic group, an aryl group, or a 5- to 20-membered heteroaryl group, wherein the 3- to 20-membered heterocyclic group, aryl group, or 5- to 20-membered heteroaryl group may optionally be fused to a 4- to 7-membered cycloalkyl group, provided that when the heterocyclic group contains an N atom, the heterocyclic group may be bonded to the carbon atom at the 2-position of the pyrimidine ring in Formula IX through its N atom or C atom; 6-20 The aryl group, or 5- to 20-membered heteroaryl group 6-20 may optionally be fused to a 4- to 7-membered cycloalkyl group, provided that when the heterocyclic group contains an N atom, the heterocyclic group may be bonded to the carbon atom at the 2-position of the pyrimidine ring in Formula IX through its N atom or C atom; R a represents H or -X-R3; X represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R3 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d4 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; R b represents H or -Y-R4; Y represents CH2, O, S, NH, -S(O)-, -S(O)2- or -C(O)-; R4 represents H, halogen, OH, CN, -CH2CF3, -NHR d4 , unsubstituted or optionally substituted by one, two or more R d5 substituted with the following groups: C 1-20 alkyl, -C(O)R 61 , -C(O)OR 62 , -OC(O)R 63 , NH2; The condition is that R a and R b are not both H at the same time; Alternatively, R a , R b together with the atom to which it is attached form an unsubstituted or optionally substituted by 1, 2 or more R d6 substituted with the following groups: C 5-20 cycloalkenyl, 3- to 20-membered heterocyclic group, 5- to 20-membered heteroaryl, 6- to 20-membered aryl; Each R d2 、R d4 、R d5 、R d6 is the same as or different from each other and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), SO, SO2, and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 31 、-CH2-C(O)R 31 、-C(O)OR 32 、-CH2C(O)OR 32 、-C(O)NHR 32 、-CH2C(O)NHR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 ); Alternatively, when there are more than two substituents selected from R d2 、R d4 、R d5 、R d6 on the same group, the two substituents may together with the atoms to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R e of the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R c is the same or different and independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), unsubstituted or optionally substituted by 1, 2 or more R e substituted with the following groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl-O-C 6-20 aryl-, 5-20 membered heteroaryl-N-C 6-20 aryl-, 5-20 membered heteroaryl-S-C 6-20 aryl-, 5-20 membered heteroaryl-CH2-C 6-20 aryl-, C 4-10 cycloalkyl-fused C 6-20 aryl-, 4-10 membered heterocycloalkyl-fused C 6-20 aryl-, 4-10 membered heterocycloalkenyl-fused C 6-20 aryl-, C 4-10 cycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkyl-C 6-20 aryl-, 4-10 membered heterocycloalkenyl-C 6-20 aryl-, 5-20 membered heteroaryl, C 4-10 cycloalkyl-fused 5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-fused 5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-fused 5-20 membered heteroaryl-, C 4-10 cycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryl-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryl-, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic aryloxy, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 Arylthio, 5- to 20-membered heteroarylthio, 3- to 20-membered heterocyclothio, NH2, -C(O)R 31 , -C(O)OR 32 , -OC(O)R 33 , -S(O)2R 34 , -S(O)2OR 35 , -OS(O)2R 36 , -P(O)(OR 37 )(OR 38 ); For example, the 4- to 10-membered heterocycloalkyl or 4- to 10-membered heterocycloalkenyl may be: 1-methylpyrrolidinyl, 1-ethylpyrrolidinyl, 1-cyclopropylpyrrolidinyl, 1-cyclopropylmethylpyrrolidinyl, 5-methyl-4,5-dihydropyridazin-3(2H)-one group, 1-methylazetidinyl, 1-methylpiperidinyl; m is an integer selected from 1 to 10; Each R e is the same or different and is independently selected from H, halogen, OH, CN, NO2, NH2, oxo (=O), thioxo (=S), O-CONH2, O-CONHR f and the following groups which are unsubstituted or optionally substituted by one, two or more Rs f : C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, C 1-8 -heteroalkyl and C 6-20- aryl-, C 1-8 -heteroalkyl-C 6-20- aryl-, NH2, -C(O)R 41 、-C(O)OR 42 、-OC(O)R 43 、-S(O)2R 44 、-S(O)2OR 45 、-OS(O)2R 46 、-P(O)(OR 47 )(OR 48 ); Alternatively, when there are more than two substituents selected from R e on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R f substituted following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R f is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R g groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocyclic oxy group, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5-20 membered heteroarylthio, 3-20 membered heterocyclic thio group, NH2, -C(O)R 51 , -C(O)OR 52 , -OC(O)R 53 , -S(O)2R 54 , -S(O)2OR 55 , -OS(O)2R 56 , -P(O)(OR 57 )(OR 58 ); Alternatively, when there are two or more substituents selected from R f on the same group, the two substituents may together with the atom to which they are attached form an unsubstituted or optionally substituted by 1, 2 or more R g substituted with the following groups: C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group; Each R g is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo(=O), thioxo(=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, NH2; Each R 31 、R 32 、R 33 、R 34 、R 35 、R 36 、R 37 、R 38 、R 41 、R 42 、R 43 、R 44 、R 45 、R 46 、R 47 、R 48 、R 51 、R 52 、R 53 、R 54 、R 55 、R 56 、R 57 、R 58 are the same or different and are each independently selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2; The 3- to 20-membered heterocyclic group represents a saturated or unsaturated non-aromatic ring or ring system, such as a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spiro ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, such as 1, 2, 3, 4, 5 or more heteroatoms independently selected from O, S and N, wherein N and S can also be optionally oxidized to various oxidation states to form the state of nitrogen oxides, -S(O)- or -S(O)2-; Said C 6-20 Aryl represents a monocyclic, bicyclic (such as a fused ring, bridged ring, spiro ring) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms and being monovalent aromatic or partially aromatic, which may be a monoaromatic ring or a polyaromatic ring fused together; The 5- to 20-membered heteroaryl represents a monovalent monocyclic, bicyclic (such as a fused ring, a bridged ring, a spiro ring) or tricyclic aromatic ring system, and the aromatic ring system has 5 to 20 ring atoms and contains 1, 2, 3, 4, 5 or more heteroatoms independently selected from N, O and S. According to an embodiment of the present disclosure, L represents an alkynyl group; a mono- or polycyclic C 6-20- aryl or a mono- or polycyclic C 6-20 -aryl and a 4- to 7-membered cycloalkyl group, which may each independently be optionally substituted at the ortho, para, or meta position by one, two, or three independent groups substituted by fluorine, chlorine, bromine, hydroxyl, CN, NH2, or by 1, 2, or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH═CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH═CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 10-membered heterocyclic-C 6-20- aryl, 3- to 10-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3- to 10-membered heterocyclic-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-10 -aryl, SO2-CH3, SO2-CH2CH3, and SO2-NR 1.2 R 1.3 substituents, and each of said substituents may in turn be optionally substituted by 1, 2, or more substituents selected from OH, OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-10- aryl, and NR 1.2 R 1.3 substituted by the substituents in L represents a group selected from heterocycles or heteroaryls, which are each independently optionally substituted in the ortho, para or meta positions by one, two or three groups of halogen, OH, oxo, CF3, CHF2 and CH2F, or by 1, 2 or more substituents selected from OR 1.1 、C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 、C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 、C 1-3 -alkyl-OR 1.1 、SR 1.1 、C 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-10 membered heterocyclic-C 6-20- aryl, 3-10 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 and the substituents of R 1.1 、oxygen, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- Aryl and NR 1.2 R 1.3 is substituted by one, two or more substituents selected from The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused ring or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaryl is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; in some embodiments, L is selected from a 5-membered monocyclic heteroaryl, a 5-membered heteroaryl-benzene ring, a 5-membered heteroaryl-5- to 10-membered heteroaryl, a 5-membered heteroaryl-4- to 7-membered cycloalkyl, a 5-membered heteroaryl-4- to 7-membered heterocycloalkyl, a 6-membered heteroaryl-benzene ring, a 6-membered heteroaryl-5- to 10-membered heteroaryl, a 6-membered heteroaryl-6-membered heteroaryl, a 6-membered heteroaryl-4- to 7-membered cycloalkyl, a 6-membered heteroaryl-4- to 7-membered heterocycloalkyl; The cycloalkyl can be saturated or partially saturated; R 1.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, C 3-11 -mono- or bicyclic heterocycle, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-10 membered heterocycle-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl; R 1.2 and R 1.3 each independently represent H or are selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20- aryl, 3-10 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 1.1 and COOR 1.1 groups, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 1.1 substituents. According to an embodiment of the present disclosure, examples of L can be selected from the following groups: According to an embodiment of the present disclosure, each R d2 is the same or different and independently represents hydrogen, halogen, cyano, hydroxy, CF3, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CHF2, CH2F, SO2-CH3, SO2-CH2CH3, SO2-NR 1.2 R 1.3 , C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2 or C 1-3 -alkyl-NHR 1.1 substituted, and each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, OR 1.1 , oxo, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 ; According to an embodiment of the present disclosure, R e may be selected from OH; Each R d6 is the same or different and independently represents H, F, Me, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, a mono- or polycyclic C 6-20- aryl or a mono- or polycyclic C 6-20 -aryl-fused 4-7-membered cycloalkyl, a mono- or polycyclic C6-20-heteroaryl-fused 4-7-membered cycloalkyl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl; or, Each R d6 is the same or different and independently represents H, F, Me, C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 1.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 1.1 , C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 6-10- aryl, C 6-10 -aryl-C 1-6 -alkyl, C 5-10 -heteroaryl-C 1-6 -alkyl, C 3-10 -heterocycle and C 5-10 -heterocycle, -NR’R”, fluorine, C 1-6- fluoroalkyl and C 1-6- fluoroalkoxy, where R’ and R” are independently selected from H and C 1-6- alkyl; the groups may in each case optionally be substituted by one, two or more substituents selected from OH, oxo, halogen, C 1-6- alkyl and O-C 1-6- alkyl. Alternatively, two atoms, together with R d6 to which they are attached, form a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged cycloalkyl, or a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocycle being unsubstituted or optionally substituted in the ortho, para or meta position by one, two or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, monocyclic or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3- to 10-membered heterocyclic-C 6-20- aryl, 3- to 10-membered heterocycle, 5- to 20-membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; R 2.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-10 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted with a group selected from OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 6-20- aryl; R 2.2 and R 2.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkylene, mono- or bicyclic C 6-20- aryl, 3-10 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 2.1 and COOR 2.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 2.1 . Each R c which is the same or different and independently of one another represents hydrogen, a mono- or polycyclic C 6-20 -aryl or a mono- or polycyclic C 6-20 -aryl and 4- to 7-membered cycloalkyl, such as C 4-10 cycloalkyl and C 6-20 aryl-, 4- to 10-membered heterocycloalkyl and C 6-20 aryl-, 4- to 10-membered heterocycloalkenyl and C 6-20 aryl-, C 4-10 cycloalkyl-C 6-20 aryl-, 4- to 10-membered heterocycloalkyl-C 6-20 aryl-, 4- to 10-membered heterocycloalkenyl-C 6-20 aryl-, 5- to 20-membered heteroaryl, C 4-10 cycloalkyl and 5- to 20-membered heteroaryl-, 4- to 10-membered heterocycloalkyl and 5- to 20-membered heteroaryl-, 4- to 10-membered heterocycloalkenyl and 5- to 20-membered heteroaryl-, C 4-10 cycloalkyl-5- to 20-membered heteroaryl-, 4- to 10-membered heterocycloalkyl-5- to 20-membered heteroaryl-, 4- to 10-membered heterocycloalkenyl-5- to 20-membered heteroaryl-, or selected from 5- to 20-membered heteroaryl-O-C 6-20 aryl-, 5- to 20-membered heteroaryl-N-C 6-20 aryl-, 5- to 20-membered heteroaryl-S-C 6-20 aryl-, 5- to 20-membered heteroaryl-CH2-C 6-20 aryl-, the abovementioned groups may each independently optionally be substituted in the ortho, para or meta position by one, two or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxyl, CN, NO2, NH2, or by 1, 2 or more substituents selected from OR 4.1 , COOR 4.1 CH2COOR 4.1 , CH2CH2COOR 4.1 , CH=CHCOOR 4.1 , CO-NR 4.1 CH2CO-NR 4.1 , CH2CH2CO-NR 4.1 , CH=CHCO-NR 4.1 , NR 4.2 R 4.3 , CH2-NR 4.2 R 4.3 , CH2CH2-NR 4.2 R 4.3 , C 1-3 -alkyl-CN, C 1-3 -alkyl-OH, C 1-3 -alkyl-OR 4.1 , C 1-3 -alkyl-NH2, C 1-3 -alkyl-NHR 4.1 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic C 6-20- aryl), 3- to 10-membered heterocyclic group-C 6-20- aryl, 3- to 10-membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3- to 10-membered heterocycle-C 1-6 -alkyl, 5- to 20-membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 4.2 R 4.3 substituted by substituents of Alternatively, each R c is the same or different and independently represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three groups selected from halogen, OH, oxo, CF3, CHF2 and CH2F, or by one, two or more substituents selected from OR 4.1 , C 1-3 -alkyl-OR 4.1 , SR 4.1 , C 1-3 -alkyl-SR 4.1 , SO-R 4.1 , C 1-3 -alkyl-SOR 4.1 , SO2-R 4.1 , C 1-3 -alkyl-SO2R 4.1 , COOR 4.1 , CH2COOR 4.1 , CH2CH2COOR 4.1 , CH=CHCOOR 4.1 , CO-NR 4.1 CH2CO-NR 4.1 , CH2CH2CO-NR 4.1 , CH=CHCO-NR 4.1 , COR 4.1 , CH2COR 4.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-10 membered heterocyclic-C 6-20- aryl, 3-10 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 4.1 and NR 4.2 R 4.3 substituted, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 4.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 4.2 R 4.3 ; The heterocycle represents a 3- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused ring or optionally bridged ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; The heteroaromatic ring is a 5- to 10-membered, monocyclic or bicyclic, optionally fused heteroaryl including 1, 2, 3 or 4 heteroatoms independently selected from N, S or O; in some embodiments, R4 is selected from a 5-membered monocyclic heteroaryl, a 5-membered heteroaryl-benzene ring, a 5-membered heteroaryl-5- to 10-membered heteroaryl, a 5-membered heteroaryl-4- to 7-membered cycloalkyl, a 5-membered heteroaryl-4- to 7-membered heterocycloalkyl, a 6-membered heteroaryl-benzene ring, a 6-membered heteroaryl-5- to 10-membered heteroaryl, a 6-membered heteroaryl-6-membered heteroaryl, a 6-membered heteroaryl-47-membered cycloalkyl, a 6-membered heteroaryl-4- to 7-membered heterocycloalkyl; The cycloalkyl can be saturated or partially saturated; R 4.1 is H or is selected from C 1-6- alkyl, C 1-6- alkyl alcohol, C 1-3 -haloalkyl, mono- or bicyclic, -C 3-10 -cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 -alkyl, 3-10 membered heterocyclic-C 1-6 -alkyl, C 3-10 -cycloalkyl-C 1-6 -alkyl, mono- or bicyclic C 6-20- aryl, 5-20 membered heteroaryl and heterocycle, which may optionally be substituted by OH, O-(C 1-3 -alkyl), halogen, C 1-10- alkyl and C 5-10 aryl substituents; R 4.2 and R 4.3 each independently represents H or is selected from C 1-6- alkyl, mono- or bicyclic C 3-10- cycloalkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, mono- or bicyclic C 6-20- aryl, 3-10 membered heterocycle, heteroaryl ring, CO-NH2, CO-NH - CH3, -CO-N(CH3)2, SO2-(C 1-3 -alkyl), CO-R 4.1 and COOR 4.1 and the group of COOR, which may optionally be substituted by one, two or more substituents selected from OH, halogen, C 1-6 -alkyl, C 6-20- aryl and COOR 4.1 ; For example, the 4- to 10-membered heterocyclic group or 4- to 10-membered heterocyclenyl group can be: 1-methylpyrrolidinyl, 1-ethylpyrrolidinyl, 1-cyclopropylpyrrolidinyl, 1-cyclopropylmethylpyrrolidinyl, 5-methyl-4,5-dihydropyridazin-3(2H)-one group, 1-methylazetidinyl, 1-methylpiperidinyl.

12. The compound, racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug according to any one of claims 1-11, wherein: R1 represents hydrogen, a mono- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three fluorine, chlorine, bromine, iodine, hydroxyl, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO - NHOH, -CO - NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, CN, NO2, NH2 substituents, or substituted by one, two or more substituents selected from OR 1.1 , COOR 1.1 CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , NR 1.2 R 1.3 , CH2-NR 1.2 R 1.3 , CH2CH2-NR 1.2 R 1.3 , C 3-10 -cycloalkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, C 1-6 -alkyl, C 1-3 -fluoroalkyl, CF3, CHF2, CH2F, C 6-20- aryl-C 1-6 -alkyl, 3-20 membered heterocyclic-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-20- aryl, SO2-CH3, SO2-CH2CH3 and SO2-NR 1.2 R 1.3 substituents, each of said substituents optionally further substituted by one, two or more substituents selected from OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO - NHOH, -CO - NHOH, -C 1-3- alkyl-NH - CO - NR 1.2 R 1.3 , -NR 1.1 CN, -CHO,, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , -OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 1.2 R 1.3 is substituted by the substituents in; wherein, R 1.1 , R 1.2 , R 1.3 has the definitions described above; Alternatively, R1 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions each by one, two or three halogen, OH, CN, NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO - NHOH, -CO - NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, nitro, oxo, CF3, CHF2 and CH2F, or substituted by one, two or more groups selected from OR 1.1 , C 1-3 -alkyl-OR 1.1 , SR 1.1 , C[[ID=2�]] 1-3 -alkyl-SR 1.1 , SO-R 1.1 , C 1-3 -alkyl-SOR 1.1 , SO2-R 1.1 , C 1-3 -alkyl-SO2R 1.1 , COOR 1.1 , CH2COOR 1.1 , CH2CH2COOR 1.1 , CH=CHCOOR 1.1 , CO-NR 1.1 CH2CO-NR 1.1 , CH2CH2CO-NR 1.1 , CH=CHCO-NR 1.1 , COR 1.1 , CH2COR 1.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 1.1 and NR 1.2 R 1.3 substituted by substituents, and each of said substituents may optionally be substituted by OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3- -alkyl-NHOH, -C 1-3- -alkyl-CO - NHOH, -CO-NHOH, -C 1-3- -alkyl-NH - CO-NR 1.2 R 1.3 、-NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 C 1-3 -alkyl-COOR 1.1 、CONHR 1.1 C 1-3 -alkyl-CONHR 1.1 、OR 2.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6- -alkyl, C 6-10- -aryl and NR 1.2 R 2.3 substituted by one, two or more substituents selected from; wherein, R 1.1 、R 1.2 、R 1.3 has the definitions as described above; Alternatively, R2 represents hydrogen, a mono- or polycyclic C 6-20 aryl, optionally and independently at the ortho, para or meta positions each optionally substituted by one, two, or three substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, CN, NO2, NH2, or substituted by 1, 2 or more substituents selected from OR 2.1 , COOR 2.1 , CH2COOR 2.1 , C(CH3)2COOR 2.1 , CF2COOR 2.1 , CHFCOOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 , CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , NR 2.2 R 2.3 , CH2-NR 2.2 R 2.3 , CH2CH2-NR 2.2 R 2.3 , C 3-10 -cycloalkyl, COOR 2.1 , -C 3-8- cycloalkyl, CO-NR 2.1 , -C 3-8- cycloalkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, C 1-6 , -alkyl, C 1-3 , -fluoroalkyl, CF3, CHF2, CH2F, C 6-20 aryl-C 1-6 , -alkyl, 3-20 membered heterocyclic-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6- alkyl, C 6-10 , -aryl, C 1-3 , -alkyl-SOR 2.1 , C 1-3 , -alkyl-SO2R 2.1 , SO2-CH3, SO2-CH2CH3 and SO2-NR 2.2 R 2.3 and the substituents of each of the foregoing substituents may in turn be optionally substituted by 1, 2 or more substituents selected from OH, CN, C 1-3 , -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3 -alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 、-NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 、C 1-3 -COOR 1.1 、CONHR 1.1 、C 1-3 -alkyl-CONHR 1.1 、OR 2.1 、oxo, halogen, CF3, CHF2, CH2F, C 1-6 -alkyl, C 6-20- aryl and NR 2.2 R 2.3 substituted by the substituents in, CCOOR 2.1 ; wherein, R 2.1 、R 2.2 、R 2.3 has the definitions described above; Alternatively, R2 represents a group selected from heterocycles and heteroaryls, which may optionally be independently substituted at the ortho, para or meta positions by one, two or three halogens, OH, CN, NH2, -NHOH, -C 1-3 -alkyl-NHOH, -C 1-3 -alkyl-CO - NHOH, -CO-NHOH, -C 1-3 -alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, nitro, oxo, CF3, CHF2 and CH2F, or substituted by one, two or more groups selected from OR 2.1 , C 1-3 -alkyl-OR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , COOR 2.1 , -C 3-8 -cycloalkyl, CO-NR 2.1 , -C 3-8 -cycloalkyl, CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 , -alkyl alcohol, mono- or bicyclic C 3-10 , -cycloalkyl, C 6-20 , aryl, C 1-6 , -alkyl, C 6-20 , -aryl-C 1-6 , -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 , -alkyl-(monocyclic or polycyclic-C 6-20 aryl), 3-20 membered heterocyclic-C 6-20 aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 , -alkyl-OR 2.1 and NR 2.2 R 2.3 is substituted by substituents, and each of said substituents may optionally be substituted by one, two or more substituents selected from OH, OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-20- aryl and NR 2.2 R 2.3 ; wherein R 2.1 , R 2.2 , R 2.3 has the definitions as described above; Alternatively, R2 and R 2’ together with the atom to which it is attached form a 4- to 11-membered, monocyclic or bicyclic, saturated or partially saturated, optionally fused or optionally bridged heterocyclic ring containing 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, said heterocyclic ring being unsubstituted or optionally substituted in the ortho, para or meta position by 1, 2 or more substituents selected from the following: halogen, OH, oxo, CF3, CHF2, CH2F, OR 2.1 , C 1-3 -alkyl-OR 2.1 , C 1-3 -alkyl-O-C 1-3 -alkyl-COOH, C 1-3 -alkyl-O-C 1-3 -alkyl-CONR 2.1 , C 1-3 -alkyl-phosphoric acid, C 1-3 -alkyl-O-C(O)-OR 2.1 , C 1-3 -alkyl-O-C(O)-NR 2.1 , C 1-3 -alkyl-O-C(=O)-C 1-3 -alkyl-(O-C 1-3 -alkyl)v, C 1-3 -alkyl-O-C(=O)-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-O-C 1-6 -alkyl-COOR 2.1 , C 1-3 -alkyl-N-C(=O)-N-C 1-6 -alkyl-COOR 2.1 , SR 2.1 , C 1-3 -alkyl-SR 2.1 , SO-R 2.1 , C 1-3 -alkyl-SOR 2.1 , SO2-R 2.1 , C 1-3 -alkyl-SO2R 2.1 , COOR 2.1 , CH2COOR 2.1 , CH2CH2COOR 2.1 , CH=CHCOOR 2.1 , CO-NR 2.1 , CH2CO-NR 2.1 , CH2CH2CO-NR 2.1 , CH=CHCO-NR 2.1 , COR 2.1 , CH2COR 2.1 , C 1-6 -alkyl alcohol, mono- or bicyclic C 3-10 -cycloalkyl, C 6-20- aryl, C 1-6 -alkyl, C 6-20- aryl-C 1-6 -alkyl, 5-20 membered heteroaryl-C 1-6 alkyl, C 1-3 -alkyl-(monocyclic or polycyclic-C 6-20- aryl), 3-20 membered heterocyclic-C 6-20- aryl, 3-20 membered heterocycle, 5-20 membered heteroaryl C 1-3 -alkyl-OR 2.1 , NR 2.2 R 2.3 , C 6-20- aryl and NR 2.2 R 2.3 ; each of said substituents may in turn be optionally substituted by one, two or more substituents selected from OH, CN, C 1-3 -alkyl-CN, C 1-3 -alkyl-NH2, -SH, -NH2, -NHOH, -C 1-3- alkyl-NHOH, -C 1-3- alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO - NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , -OR 1.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6 , alkyl, C 6-20- aryl and NR 1.2 R 1.3 wherein, R 2.1 , R 1.2 , R 1.3 , v have the definitions as described above; Alternatively, each R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 is the same as or different from one another and is independently selected from H, halogen, OH, CN, NO2, oxo (=O), thio (=S), C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, 5- to 20-membered heteroaryl, 3- to 20-membered heterocyclic group, NH2; each of the above groups may optionally be substituted by OH, CN, C 1-3 -alkyl-CN, -SH, -NH2, -NHOH, -C 1-3 -alkyl-NHOH, -C 1-3 -alkyl-CO-NHOH, -CO-NHOH, -C 1-3- alkyl-NH-CO-NR 1.2 R 1.3 , -NR 1.1 CN, -CHO, C 2-6 -alkenyl, -O-C 3-8 -cycloalkyl, COOR 1.1 , C 1-3 -alkyl-COOR 1.1 , CONHR 1.1 , C 1-3 -alkyl-CONHR 1.1 , OR 2.1 , oxo, halogen, CF3, CHF2, CH2F, C 1-6- alkyl, C 6-10- aryl and NR 1.2 R 2.3 is substituted by one, two or more substituents; wherein, R 1.1 , R 1.2 , R 2.1 , R 2.3 has the definitions described above; Alternatively, each R c is the same or different and is independently selected from H, halogen, OH, CN, NO2, oxo (=O), thioxo (=S), and the following groups which are unsubstituted or optionally substituted by 1, 2 or more R e groups: C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, C 3-20 cycloalkenyl, C 3-20 cycloalkynyl, C 6-20 aryl, C 1-6 alkyl-C 4-10 heterocycloalkyl, C 1-6 alkyl-C 4-10 heterocycloalkenyl, C 1-6 alkyl-C 6-20 aryl, C 1-6 alkyl-C 5-20 heteroaryl, 5-20 membered heteroaryloxy-C 6-20 aryloxy-, 5-20 membered heteroarylamino-C 6-20 arylsulfanyl-, 5-20 membered heteroarylsulfanyl-C 6-20 arylmethyl-C 6-20 aryloxy-, C 4-10 cycloalkyl-fused C 6-20 aryloxy-, 4-10 membered heterocycloalkyl-fused C 6-20 aryloxy-, 4-10 membered heterocycloalkenyl-fused C 6-20 aryloxy-, C 4-10 cycloalkyl-C 6-20 aryloxy-, 4-10 membered heterocycloalkyl-C 6-20 aryloxy-, 4-10 membered heterocycloalkenyl-C 6-20 aryloxy-, 5-20 membered heteroaryloxy-, 3-20 membered heterocycloalkyloxy-, C 4-10 cycloalkyl-fused 5-20 membered heteroaryloxy-, 4-10 membered heterocycloalkyl-fused 5-20 membered heteroaryloxy-, 4-10 membered heterocycloalkenyl-fused 5-20 membered heteroaryloxy-, C 4-10 cycloalkyl-5-20 membered heteroaryloxy-, 4-10 membered heterocycloalkyl-5-20 membered heteroaryloxy-, 4-10 membered heterocycloalkenyl-5-20 membered heteroaryloxy-, 3-20 membered heterocycloalkyloxy-, C 1-20 alkyloxy, C 2-20 alkenyloxy, C 2-20 alkynyloxy, C 3-20 cycloalkyloxy, C 3-20 cycloalkenyloxy, C 3-20 cycloalkynyloxy, C 6-20 aryloxy, 5-20 membered heteroaryloxy, 3-20 membered heterocycloalkyloxy, C 1-20 alkylthio, C 2-20 alkenylthio, C 2-20 alkynylthio, C 3-20 cycloalkylthio, C 3-20 cycloalkenylthio, C 3-20 cycloalkynylthio, C 6-20 arylthio, 5 - 20 - membered heteroarylthio, 3 - 20 - membered heterocyclicthio, NH2, -C(O)R 31 、-C(O)OR 32 、-OC(O)R 33 、-S(O)2R 34 、-S(O)2OR 35 、-OS(O)2R 36 、-P(O)(OR 37 )(OR 38 ); wherein, R 31 、R 32 、R 33 、R 34 、R 35 、R 36 、R 37 、R 38 has the definitions described above; Alternatively, the compound is selected from the following compounds:

13. A method for preparing the compound, racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug according to any one of claims 1-12, wherein the preparation method comprises reacting a compound of formula A1 with a compound of formula B1 to obtain a compound of formula H: And optionally, derivatizing the compound of formula G into its stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, metabolite, pharmaceutically acceptable salt or prodrug; Among them, LG is a leaving group, such as Cl, Br or I; X1, L, W, R a , R b , R c , R2, R 2’ , m each independently have the definition described in any one of claims 1-11.

14. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to any one of claims 1-12 (for example, any one of the compounds represented by formulae I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or at least one of its prodrug compounds.

15. A method for preventing or treating a disease, comprising administering to a patient in need thereof at least one of the compound according to any one of claims 1-12 (for example, one of the compounds represented by formulae I to IX), its racemate, stereoisomer, tautomer, isotope-labeled compound, solvate, polymorph, pharmaceutically acceptable salt or its prodrug compound; The disease may be a PDE4B-mediated disease, or a disease mediated at least by PDE4; Preferably, the diseases include, but are not limited to, respiratory inflammatory diseases, inflammatory bowel diseases, arthritic diseases, skin inflammatory diseases, eye inflammatory diseases, and diseases of the peripheral or central nervous system, degenerative lesions of the central nervous system, Alzheimer's Disease (AD), Non-alcoholic Steatohepatitis (NASH), Idiopathic Pulmonary Fibrosis (IPF) or pulmonary hypertension associated therewith, chronic obstructive pulmonary disease (COPD) or pulmonary hypertension associated therewith, hepatic fibrosis (HF), renal fibrosis, benign prostatic hyperplasia (BPH), gastroesophageal reflux disease, obstructive sleep apnea, and coronary artery disease or cancer; Preferably, the cancer includes, but is not limited to, one selected from the following: gastric cancer, bladder cancer, blood cancer, bone cancer, brain cancer, breast cancer, central nervous system cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, gallbladder cancer, gastrointestinal cancer, genital cancer, genitourinary cancer, head cancer, kidney cancer, laryngeal cancer, liver cancer, lung cancer, muscle tissue cancer, cervical cancer, oral or nasal mucosa cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, spleen cancer, small intestine cancer, colorectal cancer, testicular cancer, and / or thyroid cancer; Preferably, the lesions of the diseases include the respiratory system, digestive system, excretory system, and / or reproductive system, such as the lung, liver, kidney, and / or prostate.

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