Macrocyclic compound as well as pharmaceutical composition and application thereof

Abstract

The invention relates to a macrocycle-containing inhibitor, a composition and application of the macrocycle-containing inhibitor. In particular, the present invention relates to a compound represented by formula (I), a pharmaceutical composition containing the compound, and uses of the compound as an EGFR inhibitor in treatment of cancer-related diseases. # imgabs0 #

Description

Macrocyclic compound and its pharmaceutical composition and application Technical Field

[0001] The present invention belongs to the field of medicine, and in particular relates to a macrocyclic compound and a pharmaceutical composition and application thereof. Background Art

[0002] The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that belongs to the ErbB family of tyrosine kinase receptors. Activation of EGFR leads to autophosphorylation of the receptor tyrosine kinase, which initiates a cascade of downstream signaling pathways involved in regulating cell proliferation, differentiation, and survival. EGFR is aberrantly activated by various mechanisms, such as receptor overexpression, mutation, ligand-dependent receptor dimerization, and ligand-independent activation, and has been implicated in the development of multiple human cancers.

[0003] In the field of cancer, lung cancer is one of the malignant tumors with the highest growth in morbidity and mortality, and poses the greatest threat to human health and life. Therefore, the development of treatments for lung cancer is a major research focus for anti-tumor drugs. Because epidermal growth factor receptor (EGFR) is a major driver of lung cancer (mutations account for over 20% and are more prevalent in Asian populations), the development of EGFR inhibitors as targeted therapies for lung cancer patients has attracted widespread attention from drug researchers.

[0004] Among them, in non-small cell lung cancer (NSCLC), EGFR mutations account for approximately 12-47%, of which the two most common mutations are deletion mutations in exon 19 (del19) and point mutations in exon 21 (mainly L858R). The resulting abnormal activation of epidermal growth factor receptor (EGFR) that is independent of ligands promotes the proliferation of tumor cells, which is also the scientific basis for the development of EGFR inhibitors. The first generation (Gefitinib) used in clinical practice Erlotini and icotinib ), second generation (Afatinib Dacomitinib and Neratinib The objective response rate of first-generation and third-generation (osimertinib, AZD9291) EGFR inhibitors for NSCLC tumors with these two mutations is approximately 60-85%. However, this response does not last a lifetime. Usually, patients will develop varying degrees of drug resistance 9.2 to 14.7 months after taking first- or second-generation EGFR inhibitors. Of these drug-resistant mutations, approximately 50-70% occur at the gatekeeper site T790M on EGFR. This mutation can cause changes in the spatial conformation of EGFR, increase EGFR's affinity for ATP, and thus weaken the inhibitor's ability to bind to EGFR. Although the second-generation EGFR inhibitor Afatinib has inhibitory activity against the EGFR-T790M mutation in vitro, it has not been able to overcome the drug resistance caused by the T790M mutation in clinical application. Moreover, it is difficult for both first- and second-generation EGFR inhibitors to exclude inhibition of wild-type EGFR, resulting in significant skin toxicity (such as acne-like rash). This situation was not resolved until the emergence of the third-generation inhibitor osimertinib.

[0005] Although osimertinib addresses the T790M mutation, clinical studies have observed that in EGFR T790M-positive NSCLC patients receiving osimertinib as second-line treatment, drug resistance develops after 10 months of medication, with 20-40% of these patients harboring C797S mutations (i.e., cis or trans triple mutations of del19 / T790M / C797S or L858R / T790M / C797S). While osimertinib also has a positive effect on EGFR-sensitive mutations (del19 or L858R) and has been approved for first-line indications, drug-resistant mutations develop after approximately 19 months of use, 7% of which harbor C797S double mutations (i.e., del19 / C797S or L858R / C797S).

[0006] Currently, three generations of EGFR inhibitors have been approved for marketing. With their approval for first- and second-line indications, they are widely used clinically. However, drug resistance often develops after a period of use, resulting in a failure to significantly improve patients' effective survival. Therefore, there is an urgent need to develop next-generation EGFR inhibitors to meet more clinical needs.

[0007] Summary of the Invention

[0008] In order to solve the above problems, the present invention provides a macrocyclic compound that can serve as an inhibitor of various EGFR mutations for the treatment of cancer.

[0009] The macrocyclic compound provided by the present invention is a compound represented by formula (I), or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound thereof:

[0010] in,

[0011] L1, L2 are selected from chemical bonds, -CR h R i -、-NR h -, -O-, -S-, -S(=O)-, -S(=O)2-, -C(=O)-, -NR h -C(O)-, -C(O)-NR h -, -OC(=O)- or -C(=O)O-;

[0012] L3 is selected from a chemical bond, -S-, -S(=O)-, -S(=O)2-, -O-, -NR h -、-CR h R i -、 or C 3-5 Cycloalkylene; wherein the C 3-5 Cycloalkylene is optionally substituted with one or more R h replace;

[0013] Ring A and Ring B are independently selected from C 6-14 Aryl, C 3-14 carbocyclyl, 5-14 membered heteroaryl or 3-14 membered heterocyclyl;

[0014] Each R a 、R b The same or different, each independently selected from H, deuterium, halogen, -CN, oxo, NO2, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、 -OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)2R e 、-S(O)(=NRe)R f 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f、-N(R e )S(O)2R f 、-C(O)OR e 、-OC(O)R f 、-OC(O)OR g 、C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 0-6 Alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-3-14 membered heterocyclic group or -C0-6 alkylene-5-14 membered heteroaryl group; wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 0-6 Alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-C 6-14 Aryl, -C0-6 alkylene-3-14 membered heterocyclic group, -C 0-6 Alkylene-5-14 membered heteroaryl, R e 、R f and R g Optionally replaced by one or more hydrogen, deuterium, halogen, CN, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, -OR h 、-NR h R i , substituted or unsubstituted -C 0-6 Alkylene-C 3-14 Carbocyclic group, substituted or unsubstituted -C0 6 alkylene-3-14 membered heterocyclic group, -C(O)OR h 、-C(O)NR h R i replace;

[0015] Each R1 and R2 are independently selected from R h ;or

[0016] R1 and R2 together with the atoms to which they are attached form C(O), C=CR h R i 、C=NR h , 3-14 membered heterocyclic group or C 3-14 Carbocyclic group; wherein the 3-14 membered heterocyclic group and C 3-14 The carbocyclyl group is optionally substituted by one or more R h replace;

[0017] R3, R4, and R5 are selected from H, deuterium, halogen, -CN, NO2, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、-OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f 、-N(R e )S(O)2R f 、-N=S(=O)R c‘ R c” 、-C(O)OR e 、-OC(O)R f 、-OC(O)OR g 、 C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C0-6 alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-3-14 membered heterocyclic group or -C 0-6 Alkylene-5-14 membered heteroaryl; wherein, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C 0-6 Alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-3-14 membered heterocyclic group, -C0-6 Alkylene-5-14 membered heteroaryl, R c‘ 、R c” 、R e 、R f and R g Optionally, one or more R h replace; or

[0018] R3 and R4 together with the atoms to which they are attached form C 6-14 Aryl, C 3-14 carbocyclic group, 5-14 membered heteroaryl group or 3-14 membered heterocyclic group; wherein said C 6-14 Aryl, C 3-14 Carbocyclyl, 5-14 membered heteroaryl and 3-14 membered heterocyclyl are optionally substituted by t R c replace; or

[0019] R3 and R5 together with the atoms to which they are attached form C 6-14 Aryl, C 3-14 carbocyclic group, 5-14 membered heteroaryl group or 3-14 membered heterocyclic group; wherein said C 6-14 Aryl, C 3-14 Carbocyclyl, 5-14 membered heteroaryl and 3-14 membered heterocyclyl are optionally substituted by t R c replace;

[0020] Furthermore, R3, R4, and R5 are not H at the same time;

[0021] X is selected from a chemical bond, O, S, -S(=O)-, -NR h -、-(CR h R i ) 1-3 -, -C(=O)-, -NR h -C(O)-, -C(O)-NR h -, -OC(=O)-, -C(=O)O- or -S(O)2-;

[0022] Ring C is selected from the group consisting of: 6-14 Aryl, C 3-14 carbocyclyl, 5-14 membered heteroaryl or 3-14 membered heterocyclyl;

[0023] Each R c The same or different, each independently selected from H, deuterium, halogen, CN, NO2, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-5-14 membered heteroaryl, -C 0-6Alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-3-14 membered heterocyclic group, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、-OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)(=NRe)R f 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f 、-N(R e )S(O)2R f 、-C(O)OR e 、-OC(O)R f OR-OC(O)OR g ; wherein, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-5-14 membered heteroaryl, -C 0-6 Alkylene-C 3-14 Carbocyclic group, -C 0-6 Alkylene-3-14 membered heterocyclic group, R c‘ 、R c” 、R e 、R f and R g Optionally, one or more R h 、-OR h 、-NR h R i 、-C(O)OR h 、-C(O)NR h Ri 、-NR h C(O)R i replace;

[0024] R c’ and R c” are independently selected from H, C 1-6 Alkyl or C 1-6 haloalkyl; or

[0025] R c’ and R c” Together with the atoms to which they are attached, they form a 5-7 membered heterocyclic ring, which is optionally substituted by one or more R h replace;

[0026] R e 、R f 、R g 、R h 、R i are independently selected from hydrogen, deuterium, halogen, CN, OH, NH2, -COOH, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 3-14 Cycloalkyl, -O-3-14 heterocyclic group, -S-3-14 heterocyclic group, -SC 3-14 Cycloalkyl, -SC 1-6 Alkyl, -CONH2, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -NHCOC 1-6 Alkyl, -NHCOC 2-6 Alkenyl, -NHCOC 2-6 Alkenyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6 Alkynyl, -S(O)-C 3-14Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NH2, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -CHO, -C(O)-C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -C(O)OC 2-6 Alkenyl, -OC(O)-C 2-6 Alkenyl, -C(O)-C 2-6 Alkynyl, -C(O)OC 2-6 Alkynyl, -OC(O)-C 2-6 Alkynyl, -C 0-6 Alkylene-C 6-14 Aryl, -C 0-6 Alkylene-5-14 membered heteroaryl, -C 0-6 Alkylene-C 3-14 Carbocyclic or -C 0-6 Alkylene-3-14 membered heterocyclic group; wherein the -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 3-14 Cycloalkyl, -O-3-14 heterocyclic group, -S-3-14 heterocyclic group, -SC 3-14 Cycloalkyl, -SC 1-6 Alkyl, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -NHCOC 1-6 Alkyl, -NHCOC 2-6 Alkenyl, -NHCOC 2-6 Alkenyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6Alkynyl, -S(O)-C 3-14 Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -C(O)-C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -C(O)OC 2-6 Alkenyl, -OC(O)-C 2-6 Alkenyl, -C(O)-C 2-6 Alkynyl, -C(O)OC 2-6 Alkynyl, -OC(O)-C 2-6 Alkynyl, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-5-14 membered heteroaryl, -C 0-6 Alkylene-C 3-14 Cycloalkyl and -C 0-6 Alkylene-3-14 membered heterocyclic radicals are optionally replaced by one or more hydrogen, deuterium, halogen, CN, OH, NH2, -COOH, oxo, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -C(O)-C 1-6 Alkyl, -COO(C 1-6 alkyl), -OC(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -C(O)OC 2-6 Alkenyl, -OC(O)-C 2-6 Alkenyl, -C(O)-C 2-6 Alkynyl, -C(O)OC 2-6 Alkynyl, -OC(O)-C 2-6 Alkynyl, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2、-CONH2、-CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -NHCOC 1-6 Alkyl, -NHCOC2-6 Alkenyl, -NHCOC 2-6 Alkenyl-OC(=O)NH2, -OCONH(C 1-6 alkyl) or -OCON(C 1-6 Alkyl)2, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6 Alkynyl, -S(O)-C 3-14 Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NH2, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -C 0-6 Alkylene-NHC(=O)C 1-6 Alkyl, -C 0-6 Alkylene-NHC(=O)C 1-6 Haloalkyl, -C 0-6 Alkylene-NHC(=O)C 2-6 Alkenyl, substituted or unsubstituted -C 0-6 Alkylene-C 3-14 Carbocyclyl, substituted or substituted-C 0-6 Alkylene-3-14 membered heterocyclic substitution;

[0027] m is 0, 1, 2, or 3;

[0028] n is 0, 1, 2, or 3;

[0029] r is 0, 1, 2, 3, 4, or 5;

[0030] t is 0, 1, 2, or 3.

[0031] In some embodiments, R3 in formula (I) is

[0032] M1, M3, M4, M7, M8 and M9 are independently selected from CR c , CR c R c , N or NR c ;

[0033] M2, M5, M6, M 10 Independently selected from absence, CR c R c 、-CR c R c -CR cR c - or NR c .

[0034] In some embodiments, L1 in formula (I) is selected from a chemical bond, -CH2-, -NH-, -O-, -S-, -C(=O)-, -NHC(=O)-, -C(=O)NH-, -OC(=O)-, or -C(=O)O-.

[0035] In some embodiments, L1 in formula (I) is selected from a chemical bond, -CH2- or -NHC(=O)-.

[0036] In some embodiments, L1 in formula (I) is selected from -CH2-.

[0037] In some embodiments, L2 in formula (I) is selected from a chemical bond, -O-, -S-, -NH- or -C(=O)-.

[0038] In some embodiments, L2 in formula (I) is selected from a chemical bond or -O-.

[0039] In some embodiments, L3 in formula (I) is selected from a chemical bond, -NH-, -O-, -S-, -CH2-,

[0040] In some embodiments, L3 in formula (I) is selected from a chemical bond or -NH-.

[0041] In some embodiments, ring A in formula (I) is selected from C 8-14 Bicyclic aryl or 7-14 membered bicyclic heteroaryl.

[0042] In some embodiments, Ring A in Formula (I) is selected from

[0043] In some embodiments, ring A in formula (I) is selected from C 3-8 Monocyclic carbocyclic group, 3-8 membered monocyclic heterocyclic group, C 6-8 monocyclic aryl and 5- to 8-membered monocyclic heteroaryl.

[0044] In some embodiments, Ring A in Formula (I) is selected from

[0045] In some embodiments, Ring A in Formula (I) is selected from a benzene ring or a 5-7 membered heteroaryl ring.

[0046] In some embodiments, Ring A in Formula (I) is selected from a benzene ring or a 6-membered heteroaryl ring.

[0047] In some embodiments, Ring A in Formula (I) is selected from

[0048] In some embodiments, in formula (I) Selected from

[0049] In some embodiments, in formula (I) Selected from

[0050] In some embodiments, Ring B in Formula (I) is a 5-7 membered monocyclic heteroaryl, an 8-10 membered bicyclic heteroaryl, or an 8-10 membered bicyclic heterocyclyl.

[0051] In some embodiments, Ring B in Formula (I) is a benzene ring, pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, pyrrole, thiophene, imidazole, oxazole, isoxazole, furan, thiazole, or isothiazole.

[0052] In some embodiments, Ring B in Formula (I) is a 5-membered or 6-membered monocyclic heteroaryl group containing 1-3 independently selected N atoms, a 5-membered or 6-membered bicyclic heteroaryl group containing 1-4 independently selected N atoms, a 5-membered or 6-membered bicyclic heteroaryl group containing 1-4 independently selected N atoms, or a 5-membered or 6-membered bicyclic heterocyclyl group containing 1-4 independently selected N atoms.

[0053] In some embodiments, Ring B in Formula (I) is

[0054] In some embodiments, Ring B in Formula (I) is

[0055] In some embodiments, in formula (I) for

[0056] In some embodiments, R in formula (I) a H, D, halogen, -CN, -NH2, -OH, -C(=O)OH, -C(=O)NH2, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 Alkyl; wherein the C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 The alkyl group is optionally substituted with one or more halogen, -CN, -NH2, -OH.

[0057] In some embodiments, R in formula (I) a H, D, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, halogen, -CN, C 3-6 Cycloalkyl, amino, cyano substituted C 1-3 Alkyl, -OH, -C(=O)OH, -C(=O)NH2, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 alkyl.

[0058] In some embodiments, R in formula (I) a H, D, F, Cl, Br, -CN, -NH2, C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 2-4 Alkynyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl or cyano substituted C 1-3 alkyl.

[0059] In some embodiments, R in formula (I) a For H, D, CH3, CD3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -C≡CH, OCH3, CF3, F, Cl, -NH2 or -CN.

[0060] In some embodiments, R in formula (I) a is H or CH3.

[0061] In some embodiments, R1 or R2 in formula (I) are independently selected from H, C 1-6 Alkyl, deuterated C 1-6 Alkyl, hydroxyl, C 1-6 Haloalkyl, halogen, amino, C 1-6 Alkoxy or C 1-6 Halogenated alkoxy.

[0062] In some embodiments, R1 or R2 in formula (I) are independently selected from H or C 1-3 alkyl.

[0063] In some embodiments, R1 and R2 in formula (I) together with the atoms to which they are attached form

[0064] In some embodiments, R4 in formula (I) is H, halogen, cyano, -NH2, -OH, -C(=O)OH, -C(=O)NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl, -C(O)C 1-6 Alkyl, C 6-10 aryl, 5-10 membered heterocyclic group or 5-10 membered heteroaryl; wherein, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl, -C(O)C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heterocyclyl and 5-10 membered heteroaryl are optionally substituted by one or more R h replace.

[0065] In some embodiments, R4 in formula (I) is H, halogen, -NH2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-6 Cycloalkyl, cyano or 8-10 membered heterocyclic group; wherein the 8-10 membered heterocyclic group can be optionally replaced by -C(O)-C 2-4 Alkenyl substitution.

[0066] In some embodiments, R4 in formula (I) is H, CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -C≡CH, OCH3, CF3, F, Cl, -NH2, -CN,

[0067] In some embodiments, R4 in formula (I) is H,

[0068] In some embodiments, R4 in formula (I) is H.

[0069] In some embodiments, R5 is H, halogen, -NH2, -OH, -C(=O)OH, -C(=O)NH2, -N=S(=O)(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 1-6 Alkylene cyano, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-7 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein said -NH2, -OH, -C(=O)OH, -C(=O)NH2, -N=S(=O)(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 1-6 Alkylene cyano, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-7 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl is optionally substituted by one or more R h replace.

[0070] In some embodiments, R5 is H, halogen, C 1-6 Alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl, 4-6 membered heterocyclic group, C 1-6 Alkoxy, -NH-4-membered heterocycle, -OC(O)NH-6-membered heterocycle; wherein the C 1-6 Alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl, 4-6 membered heterocyclic group, C 1-6 Alkoxy, -NH-4-membered heterocycle, -OC(O)NH-6-membered heterocycle are optionally substituted with one or more OH, NH2, oxo, C1-6 Alkyl, C 1-6 Alkoxy, -S(O)2-C 1-6 Alkyl, -C 1-6 Alkylene-S(O)2-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 substituted.

[0071] In some embodiments, R5 is H, F, Cl, NH2, CN, CH3, -N(CH3)2,

[0072] In some embodiments, R5 is H.

[0073] In some embodiments, X in formula (I) is a chemical bond, -S-, -NH-, -CH2-,

[0074] In some embodiments, X in formula (I) is a chemical bond.

[0075] In some embodiments, R in formula (I) b H, D, halogen, -CN, -OH, -NH2, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, -SC 1-6 Alkyl, -S(=O)-C 1-6 Alkyl, -S(=O)2-C 1-6 Alkyl, -S(=O)2-C 3-6 Cycloalkyl or -O-3-6 membered heterocyclic group.

[0076] In some embodiments, R in formula (I) b For H, D, F, Cl, -OCH3, CH3, CD3, CF3, CN, NH2, -S-CH3, -S(=O)-CH3,

[0077] In some embodiments, R in formula (I) b H, deuterated C 1-3 Alkyl or C 1-3 Alkyl; preferably, R b is H or CH3.

[0078] In some embodiments, Ring C in Formula (I) is absent, 5-10 membered aryl, 3-13 membered carbocyclyl, 5-14 membered heteroaryl, or 4-14 membered heterocyclyl.

[0079] In some embodiments, Ring C in Formula (I) is absent, a benzene ring, a 5-membered monocyclic carbocyclyl, a 6-membered monocyclic carbocyclyl, a 4-membered monocyclic heterocyclyl, a 5-membered monocyclic heterocyclyl, a 6-membered monocyclic heterocyclyl, an 8-membered bicyclic heterocyclyl, a 9-membered bicyclic heterocyclyl, a 10-membered bicyclic heterocyclyl, an 11-membered bicyclic heterocyclyl, a 12-membered tricyclic heterocyclyl, a 13-membered tricyclic heterocyclyl, or a 14-membered tricyclic heterocyclyl.

[0080] In some embodiments, ring C in formula (I) is absent,

[0081] In some embodiments, Ring C in Formula (I) is a 9-14 membered bicyclic heterocyclyl or a 9-14 membered tricyclic heterocyclyl.

[0082] In some embodiments, Ring C in Formula (I) is a 9-membered bicyclic spiro heterocyclyl, a 10-membered bicyclic spiro heterocyclyl, or an 11-membered bicyclic spiro heterocyclyl.

[0083] In some embodiments, Ring C in Formula (I) is

[0084] In some embodiments, Ring C in Formula (I) is

[0085] In some embodiments, R3 in formula (I) is

[0086] In some embodiments, R3 in formula (I) is

[0087] In some embodiments, R in formula (I) c H, deuterium, halogen, CN, oxo, OH, -NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, -C(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -COOH, -C 0-6 Alkylene-CONH2, -NHC(O)-C 2-6 Alkenyl, -C 1-6 Alkylene NHC(O)-C 2-6 Alkenyl, -S(=O)2-C 1-6 Alkyl, -S(=O)(=NH)-C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, phenyl, 5-6 membered heteroaryl or 3-11 membered heterocyclic group; wherein the OH, -NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, -C(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -COOH, -C 0-6 Alkylene-CONH2, -NHC(O)-C 2-6 Alkenyl, -C 1-6 Alkylene NHC(O)-C 2-6 Alkenyl, -S(=O)2-C 1-6 Alkyl, -S(=O)(=NH)-C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, phenyl, 5-6 membered heteroaryl or 3-11 membered heterocyclic group may be optionally substituted by one or more halogen, OH, CN, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -NH2, -COOH, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -CONH2, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -S(=O)2-C 1-6 Alkyl, substituted or unsubstituted -CO-3-6 membered heterocyclic group, -OC 1-6 Haloalkyl, -OC(=O)NH2, -OCONH(C 1-6 alkyl) or -OCON(C 1-6 alkyl)2 substituted.

[0088] In some embodiments, R in formula (I) cH, D, CH3, CD3, CH2CH3, CH(CH3)2, -C(CH3)3, -OH, F, Cl, oxo, NH 2、

[0089] In some embodiments, R3 in formula (I) is H, F, -CH 3、 Cl, -OCH3,

[0090] In some embodiments, m in formula (I) is 0, 1 or 2.

[0091] In some embodiments, n in formula (I) is 0, 1 or 2.

[0092] In some embodiments, r in formula (I) is 2, 3 or 4.

[0093] In some embodiments, t in formula (I) is 0, 1 or 3.

[0094] In some embodiments, in formula (I) for

[0095] M1, M3, M4, M7, M8 and M9 are independently selected from CR c , CR c R c , N or NR c ;

[0096] M2, M5, M6, M 10 Independently selected from absence, CR c R c 、-CR c R c -CR c R c - or NR c .

[0097] In some embodiments, the compound of formula (I) is selected from the compounds of formula (II) or formula (III) shown below:

[0098] in,

[0099] M1-M in the compounds of formula (II) and formula (III) 10 , L1, L2, L3, Ring B, R a 、R b, R1, R2, R4, m, n and r are as defined above in formula (I).

[0100] In some embodiments, the compound of formula (I) is selected from the compound of formula (IV) shown below:

[0101] in,

[0102] M1-M in the compound of formula (IV) 10 、R a 、R b , n and r are as defined above in formula (I).

[0103] In some embodiments, the compound of formula (I) is selected from the compounds of formula (V) or formula (VI) shown below:

[0104] in,

[0105] Q1, Q2, Q3 and Q4 are independently selected from CR b or N;

[0106] Q5 and Q6 are independently selected from N or C;

[0107] M1-M in the compound of formula (V) or formula (VI) 10 , L1, L2, Ring A, R a 、R b , R1, R2, R4, m and r are as defined above in formula (I).

[0108] In some embodiments, the compound of formula (I) is selected from the compounds of formula (VII) or formula (VIII) shown below:

[0109] in,

[0110] Q1, Q2, Q3 and Q4 are independently selected from CR b or N;

[0111] Q5 and Q6 are independently selected from N or C;

[0112] M1-M in the compound of formula (VII) or formula (VIII) 10 , L1, L2, Ring A, R a 、R b , R1, R2, R4, R5, m and r are as defined above in formula (I).

[0113] In some embodiments, the compound of formula (I) is selected from the compound of formula (IX) shown below:

[0114] in,

[0115] M1-M in the compound of formula (IX) 10 , L1, L2, R a 、R b , R1, R2, R4, R5, m, n and r are as defined above in formula (I).

[0116] In some embodiments, the compound of formula (I) is selected from the compound of formula (X) shown below:

[0117] in,

[0118] R3 is -OC(O)NHR f 、-OC(O)R f 、-C(O)NHR f ;

[0119] R f C 1-6 alkyl, 4-membered heterocyclic group, 5-membered heterocyclic group, 6-membered heterocyclic group, 7-membered heterocyclic group, 8-membered heterocyclic group, 9-membered heterocyclic group, 10-membered heterocyclic group, 11-membered heterocyclic group; wherein, the C 1-6 Alkyl, 4-membered heterocyclyl, 5-membered heterocyclyl, 6-membered heterocyclyl, 7-membered heterocyclyl, 8-membered heterocyclyl, 9-membered heterocyclyl, 10-membered heterocyclyl, 11-membered heterocyclyl are optionally substituted with one or more halogen, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 substituted;

[0120] Ring B, R in the compound of formula (X) a 、R b , R5, m and n are as defined above in formula (I).

[0121] In some embodiments, R3 in formula (X) is -OC(O)NR e R f 、-OC(O)R f 、-C(O)NR e R f ; Among them, R e H; R f for

[0122] In some embodiments, R3 in formula (X) is

[0123] In some embodiments, the compound of formula (X) is selected from the compound of formula (XI) shown below:

[0124] in,

[0125] Q1, Q2, Q3 and Q4 are independently selected from CR b or N;

[0126] R in the compound of formula (XI) a 、R b , R3 and m are as defined above in formula (X).

[0127] In some embodiments, the compound of formula (X) is selected from the compound of formula (XII) shown below:

[0128] in,

[0129] R in the compound of formula (XII) a 、R b , R3, m and n are as defined above in formula (X).

[0130] In some embodiments, the compound represented by formula (I) is selected from:

[0131] 1 1 , 2 6 -Dimethyl-5- 6 -(3-((methylsulfonyl)methyl)azetidin-1-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridinyl-1(4,5)-pyrazolocycloundecyl-3-one;

[0132] 1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,7-diazaspiro[3.5]nonan-7-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridinyl-1(4,5)-pyrazolocycloundecyl-3-one;

[0133] 5 7 -(2-acryloyl-2,7-diazaspiro[3.5]non-7-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0134] 1 1 , 2 6 -Dimethyl-5- 6 -(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0135] 5 6 -(2-acryloyl-2,7-diazaspiro[3.5]non-7-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0136] N-(4-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)cyclohex-3-en-1-yl)acrylamide;

[0137] 1 1 , 2 6 -Dimethyl-5- 6 -((1-methylpiperidin-4-yl)thio)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0138] 1 1 , 2 6 -Dimethyl-5- 6 -((4-methylpiperazin-1-yl)amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0139] 5 6 -(4-hydroxycyclohex-1-en-1-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0140] 1 1 , 2 6 -Dimethyl-5- 6 -((1'-methyl-[1,4'-dipiperidinyl]-4-yl)thio)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0141] (S)-2-(4-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-1-methylpiperazin-2-yl)acetonitrile;

[0142] 1 1 , 2 6 -Dimethyl-5- 6 -((4-(1-(methylsulfonyl)azetidin-3-yl)piperazin-1-yl)methyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0143] 1 1 , 2 6 -Dimethyl-5- 6 -(3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0144] 1 1 , 2 6-Dimethyl-5- 6 -(thiomorpholinomethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0145] 1 1 , 2 6 -Dimethyl-5- 6 -(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1 1 H, 5 1 H-11-oxa-4,6-diaza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3,7-dione;

[0146] (S)-N-(2-(4-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-1-methylpiperazin-2-yl)ethyl)acrylamide;

[0147] 1 1 , 2 6 -Dimethyl-5- 6 -(morpholinomethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0148] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0149] (S)-5 6 -(1-amino-1,3-dihydrospiro[indene-2,4'-piperidin]-1'-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0150] N-(2-((1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)(4-methylpiperazin-1-yl)amino)ethyl)acrylamide;

[0151] 5 6 -((2-methoxy-4-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)phenyl)amino)-1- ... 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0152] 1 1 , 2 6 -Dimethyl-5- 6 -(2,9-diazaspiro[5.5]undec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0153] Diethyl (E)-(1 1 , 2 6 -Dimethyl-3-oxo-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)phosphonate;

[0154] 1 1 -methyl-5 6 -(1-methyl-1,9-diazaspiro[5.5]undec-9-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0155] (E)-5 6 -(2-Acryloyl-2,9-diazaspiro[5.5]undec-9-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0156] (E)-1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,9-diazaspiro[5.5]undec-9-yl)-5 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0157] 5 6 -(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinane-2-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-3-one;

[0158] 5 6 -(1-acryloyl-1,9-diazaspiro[5.5]undec-9-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0159] 1 1 , 2 6 -Dimethyl-5- 6-(9-(2,2,2-trifluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0160] 2-(9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)acetonitrile;

[0161] 2 6 -Methoxy-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0162] 5 6 -(9-ethyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0163] 5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0164] 5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 26 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0165] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0166] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0167] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrimidin-1(4,5)-pyrazolocycloundecyl-3-one;

[0168] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0169] 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0170] 2 6 -Chloro-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0171] 2 6 -cyclopropyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0172] 2 6 -Amino-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0173] 2 6 -ethynyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0174] 2 6 -ethyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0175] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolecycloundecyl-2 6 -nitrile;

[0176] 2 6 -Isopropyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0177] 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[5.5]undec-8-en-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0178] 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[5.5]undec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0179] (S)-1 1 , 2 6 , 5 7 -Trimethyl-5 5 , 5 5a , 5 6 , 5 7 , 5 8 , 5 9 -Hexahydro-11 H, 5 3 H-11-oxa-4-aza-5(2,3)-imidazo[4′,5′:5,6]benzo[1,2-b]pyrazino[1,2-d][1,4]oxazine-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-3-one;

[0180] (S)-1 1 , 2 6 , 5 3 -Trimethyl-5 1 , 5 2 , 5 3 , 5 4 , 5 4a , 5 5 -Hexahydro-1 1 H, 5 10 H-11-oxa-4-aza-5(9,10)-imidazo[4′,5′:4,5]benzo[1,2-b]pyrazino[1,2-d][1,4]oxazine-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-3-one;

[0181] (5 5a S, 5 7 R)-5 7 -(dimethylamino)-1 1 , 2 6 -Dimethyl-5- 5a , 5 6 , 5 7 , 5 8 -Tetrahydro-1 1 H, 5 3 H, 5 5 H-11-oxa-4-aza-5(2,3)-imidazo[4′,5′:5,6]benzo[1,2-b]pyrrolo[1,2-d][1,4]oxazino-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0182] (R)-1 1 , 2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0183] 1 1 , 2 6 -Dimethyl-5- 6-((4-methylpiperazin-1-yl)sulfonyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0184] 1 1 , 2 6 -Dimethyl-5- 6 -((2-methyl-2,7-diazaspiro[3.5]nonan-7-yl)sulfonyl)-1- 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0185] 5 6 -(7-fluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0186] 5 6 -(7-hydroxy-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0187] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-2,9-diazabispiro[3.2.3 7 .2 4 ] dodec-2-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0188] (Z)-2 6 -methyl-5 6-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 , 1 5 , 1 6 , 1 7 -Tetrahydro-5 1 H-4-aza-1(3,5)-[1,2,3]triazolo[1,5-a]pyrazine-5(2,1)-benzo[d]imidazo-2(2,4)-pyridinylcyclononane-3-one;

[0189] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(3,4)-triazolocycloundecyl-3-one;

[0190] (1 3 Z, 1 4 E, 5 2 Z)-2 6 -methyl-5 6 -((4-methylpiperazin-1-yl)methyl)-5-(4-methylpiperazin-1-yl)methyl)- 2 , 5 3 -Dihydro-5 1 H-9-oxa-4-aza-1(3,5),5(2,1)-dipyrazolo[1,5-a]pyrido-2(2,4)-pyridocyclononane-3-one;

[0191] 1 1 , 2 6 -Dimethyl-5- 6 -(3-oxaspiro[5.5]undec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0192] 5 6 -((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0193] 1 1, 2 6 -Dimethyl-5- 6 -(9-methyl-2-oxo-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0194] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazo-1(7,1)-imidazo[1,2-b]pyrazol-2(2,4)-pyridocyclodecane-3-one;

[0195] 1 1 , 3 6 -Dimethyl-6 6 -((4-methylpiperazin-1-yl)methyl)-1 1 H, 6 1 H-10-oxa-2,5-diaza-6(2,1)-benzo[d]imidazo-3(2,4)-pyrido-1(3,4)-pyrazolocyclodecanyl-4-one;

[0196] 3 6 -methyl-6 6 -((4-methylpiperazin-1-yl)methyl)-6- 1 H-10-oxa-2,5-diaza-6(2,1)-benzo[d]imidazol-1(2,3),3(2,4)-bipyridocyclodecanyl-4-one;

[0197] 3 6 -methyl-6 6 -((4-methylpiperazin-1-yl)methyl)-6- 1 H-10-oxa-2,5-diaza-6(2,1)-benzo[d]imidazol-1,3(2,4)-bipyridocyclodecane-4-one;

[0198] 3 6 -methyl-6 6 -((4-methylpiperazin-1-yl)methyl)-6- 1 H-11-oxa-2,5-diaza-6(2,1)-benzo[d]imidazol-1,3(2,4)-bipyridocycloundecyl-4-one;

[0199] 3 6 -methyl-66 -((4-methylpiperazin-1-yl)methyl)-6- 1 H-12-oxa-2,5-diaza-6(2,1)-benzo[d]imidazol-1,3(2,4)-bipyridocyclododecane-4-one;

[0200] 2 6 -methyl-5 6 -((4-methylpiperazin-1-yl)methyl)-1 1 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazo-1(7,1)-imidazo[1,2-b]pyrazol-2(2,4)-pyridocyclodecanyl-3-one;

[0201] (1 3 Z, 1 4 E, 5 2 Z)-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 2 , 5 3 -Dihydro-5 1 H-9-oxa-4-aza-1(3,5),5(2,1)-dipyrazolo[1,5-a]pyrido-2(2,4)-pyridocyclononane-3-one;

[0202] 2 6 -methyl-5 6 -((4-methylpiperazin-1-yl)methyl)-1 4 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(3,4)-triazolocycloundecyl-3-one;

[0203] (Z)-2 6 -methyl-5 6 -((4-methylpiperazin-1-yl)methyl)-1 4 , 1 5 , 1 6 , 1 7 -Tetrahydro-5- 1 H-4-aza-1(3,5)-[1,2,3]triazolo[1,5-a]pyrazine-5(2,1)-benzo[d]imidazol-2(2,4)-pyridinylcycloundecyl-3-one;

[0204] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-11 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0205] 1 1 , 2 6 -Dimethyl-5- 6 -(8-methyl-2,8-diazaspiro[5.5]undec-2-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0206] 5 6 -(9-ethyl-2,9-diazaspiro[5.5]undec-2-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0207] 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3,9-diazaspiro[5.6]dodec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0208] 5 6 -(9-(dimethylamino)-3-azaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0209] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-2,9-diazaspiro[5.5]undec-2-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0210] 1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazolo-2(1,3)-benzocycloundecan-3-one;

[0211] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0212] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 6 -nitrile;

[0213] 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0214] 2 6 -Methoxy-1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0215] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one;

[0216] 1 5 -Fluorine-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one;

[0217] 1 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(3,2)-pyrrolocycloundecan-3-one;

[0218] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(3,2)-pyrrolocycloundecane-1 5 -nitrile;

[0219] (S)-1 1 , 2 6 , 5 3 -Trimethyl-5 1 , 5 2 , 5 3 , 5 4 , 5 4a , 5 5 -Hexahydro-1 1 H, 5 8H-11-oxa-4-aza-5(9,8)-imidazo[4′,5′:4,5]benzo[1,2-b]pyrazino[1,2-d][1,4]oxazine-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0220] (E)-5 6 -(9-cyclopentyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0221] (E)-5 6 -(9-acetyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0222] (E)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0223] 5 6 -(9-cyclobutyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0224] 11 , 2 6 -Dimethyl-5- 6 -(3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0225] 5 6 -(1-fluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0226] (Z)-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-2(7,5),5(2,1)-dipyrazolo[1,5-a]pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0227] 1 1 ,2 6 -Dimethyl-5- 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0228] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 2 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(7,5)-indolo-1(4,5)-pyrazolocycloundecan-3-one;

[0229] (Z)-1 1 -methyl-5 6-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-2(8,6),5(2,1)-diimidazo[1,2-a]pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0230] 1 1 , 2 1 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 2 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(7,5)-indolo-1(4,5)-pyrazolocycloundecan-3-one;

[0231] 1 1 , 2 6 -Dimethyl-5- 6 -(7-methyl-7,12-diazabispiro[2.0.5 4 .4 3 ]tridec-12-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0232] 1 1 , 2 6 -Dimethyl-5- 6 -(12-methyl-7,12-diazabispiro[2.0.5 4 .4 3 ]tridec-7-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0233] 5 6 -(1,1-difluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0234] 56 -(7,7-difluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0235] 1 1 , 2 6 -Dimethyl-5- 6 -(1'-methyl-5-azaspiro[bicyclo[2.2.1]heptane-2,4'-piperidin]-5-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0236] 1 1 , 2 6 -Dimethyl-5- 6 -(5-methyl-5-azaspiro[bicyclo[2.2.1]heptane-2,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0237] 1 1 , 2 6 -Dimethyl-5- 6 -(1'-methyl-5-azaspiro[bicyclo[2.2.2]octane-2,4'-piperidin]-5-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0238] 1 1 , 2 6 -Dimethyl-5- 6 -(5-methyl-5-azaspiro[bicyclo[2.2.2]octane-2,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0239] 11 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0240] 1 1 , 2 6 -Dimethyl-5- 6 -(1'-methyl-3-azaspiro[bicyclo[3.1.1]heptane-6,4'-piperidin]-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0241] 1 1 , 2 6 -Dimethyl-5- 6 -(1'-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0242] 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[bicyclo[3.1.1]heptane-6,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0243] 5 6 -(hexahydro-1H-spiro[indolizine-7,4'-piperidinyl]-1'-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0244] 11 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,10-diazabispiro[3.2.5 7 .2 4 ]Tetradec-10-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0245] 1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,9-diazabispiro[3.1.5 6 .1 4 ] dodec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0246] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-methyl-2-azabicyclo[2.2.1]heptane-5-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0247] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyl-3-azabicyclo[3.1.1]heptane-6-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0248] (E)-1 1 ,2 6 -Dimethyl-5- 6 -(9-(1-methylpiperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 2 ,5 3 -Dihydro-11 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0249] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(5-methyl-5-azaspiro[2.5]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0250] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(octahydroindolizin-7-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0251] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0252] 5 6 -(9-(2-cyclopropylethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0253] 1 1 , 2 6 -Dimethyl-5- 6-(9-(oxepan-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0254] 5 6 -(9-(4-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0255] 5 6 -(9-(4-hydroxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0256] 5 6 -(9-(4-methoxy-4-methylpentan-2-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0257] 1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H,5 3 H-11-oxa-4-aza-5(2,3)-imidazo[4,5-b]pyridine-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0258] 5 6-(9-(8-oxabicyclo[3.2.1]octan-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0259] 5 6 -(9-(2-hydroxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0260] 2 6 -Fluorine-2 5 -Methoxy-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0261] 2 6 -Fluorine-1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0262] 2 5 ,2 6 -Difluoro-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzoic acid cycloundecane-3-one;

[0263] 5 7 -Chloro-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0264] 1 1 , 2 6 ,9,9-tetramethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0265] 5 5 -Fluorine-1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0266] 5 7 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0267] 1 1 , 2 6 , 5 5 -Trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0268] 1,1',6'-trimethylspiro[piperidin-4,7'-11-oxa-4-aza-5(2,1)-imidazo[4',5':5,6]benzo[1,2-b][1,4]oxazine-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecane]-3'-one;

[0269] 1,1',6'-trimethylspiro[piperidin-4,7'-11-oxa-4-aza-5(2,1)-chromeno[7,8-d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecane]-3'-one;

[0270] 1 1 , 2 6 , 5 9 -Trimethyl-5 1 , 5 6 , 5 6a , 5 7 , 5 8 , 5 9 , 5 10 , 5 10a -Octahydrogen-1 1 H-11-oxa-4-aza-5(2,1)-imidazo[4′,5′:7,8]chromeno[2,3-c]pyrido-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0271] 1 1 , 2 6 , 5 8 -Trimethyl-5 5b , 5 6 , 5 7 , 5 8 , 5 9 , 5 9a -Hexahydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-imidazo[4′,5′:6,7]benzofuro[2,3-c]pyrido-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0272] 5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0273] 5 6 -(9-(2-(hydroxymethyl)cyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0274] 5 6 -(9-(2-hydroxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0275] 5 6 -(9-(3-Hydroxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0276] 5 6 -(9-(3-Hydroxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0277] 5 6 -(9-(2-hydroxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0278] 5 6 -(9-(4-isopropoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0279] 5 6 -(9-(3-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0280] 5 6 -(9-(4-ethoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0281] 5 6 -(9-(3-Hydroxycyclopentyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0282] 5 6 -(9-(1-cyclopropylpiperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0283] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(1-(oxetane-3-yl)piperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0284] 5 6 -(3'-oxa-3,9-diaza[3,9'-bispiro[5.5]undecane]-9-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0285] 1 1 -(cyclopropylsulfonyl)-2- 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0286] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(tetrahydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0287] 2 6 -Fluorine-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0288] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 5 -nitrile;

[0289] 1 5 -Methoxy-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one;

[0290] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(7,5)-benzofurancycloundecan-3-one;

[0291] 1 5 -Fluorine-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one;

[0292] 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -Fluoro-11-methyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0293] 3-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3-azaspiro[5.5]undecane-9-carboxylic acid;

[0294] 9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3,9-diazaspiro[5.5]undecane-3-carboxamide;

[0295] 2-(9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)cyclopentane-1-carboxylic acid;

[0296] 2 6 -Fluoro-5 5 -Methoxy-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0297] 1 5 , 2 6 -Difluoro-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-1 1 -Oxa-4-aza-5(2,1)-benzo[d]imidazol-1(1,2),2(1,3)-dibenzocycloundecane-3-one;

[0298] 26 -Fluorine-1 1 -methyl-5 6 -(9-(oxepan-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0299] 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 5 -nitrile;

[0300] 2 5 -Chloro-2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0301] 5 5 -Methoxy-1 1 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0302] 2 5 -Amino-2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-11H,5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0303] 5 5 -Methoxy-1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0304] 5 5 -Chloro-2 6 -Fluorine-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0305] 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-26-fluoro-1 1 , 5 5 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0306] 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 -Trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0307] 2 6 -Fluorine-1 1 , 5 5 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one;

[0308] 1 1 , 2 6 , 5 5 -Trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0309] 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-5- 5 -Fluorine-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0310] 5 5 -Chloro-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0311] 5 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0312] 5 5 -ethynyl-1 1 , 2 6 -Dimethyl-5- 6-(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0313] 5 5 -Amino-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0314] 5 5 -(dimethylamino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0315] 5 5 -((2-methoxyethyl)(methyl)amino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0316] 5 5 -Hydroxy-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0317] 5 5 -cyclobutoxy-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0318] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 5 -nitrile;

[0319] 5 5 -(cyclobutylamino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0320] 5 5 -((2-(dimethylamino)ethyl)amino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0321] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 5 - methyl carboxylate;

[0322] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-nitropropane 5 -formamide;

[0323] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0324] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(tetrahydro-2H-thiopyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0325] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methylsulfonyl)-3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0326] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methylsulfonyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0327] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(S-methylsulfonylimino)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0328] 1 4 ,1 5 -Difluoro-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undecen-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0329] 1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(Oxa-3-amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0330] (R)-1 1 ,2 6 ,7-trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0331] 9-(1 1 ,2 6 -Dimethyl-3-oxo-1 1 H, 5 1H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3,9-diazaspiro[5.5]undecane-3-carbaldehyde;

[0332] 1 1 ,2 6 -Dimethyl-5- 6 -(9-(pyrrolidin-1-yl)-3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one;

[0333] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-2-one;

[0334] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-(methylsulfonyl)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0335] 1 1 ,2 2 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(4,6)-pyrimidin-1(4,5)-pyrazolocycloundecan-3-one;

[0336] 2 5 -Methoxy-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0337] 2 5 -Fluorine-1 1 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0338] 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecyl-3-one;

[0339] 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(6,7)-furo[3,2-b]pyridine-5(2,1)-benzo[d]imidazol-2(2,4)-pyridoylundecyl-3-one;

[0340] 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one;

[0341] 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-1 5 -carbonitrile;

[0342] 1 5-Amino-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one;

[0343] 2 6 -methyl-1 2 -(methylthio)-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one;

[0344] 2 6 -methyl-1 2 -(methylsulfonyl)-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecyl-3-one;

[0345] 1 2 -Chloro-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazolyl[5.5]undecane-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one;

[0346] 1 2 ,1 6 ,2 6 -Trimethyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one;

[0347] 1 2 ,2 6 -Dimethyl-5- 6-(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-5-(9-oxetane-3-yl)-3,9-diazaspiro[5.5]undecane-3-yl)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2-(2,4)-pyridocycloundecan-4-one;

[0348] 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(2,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one;

[0349] 5 6 -(9-(3,3-difluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0350] 5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0351] 1 1 ,2 6 -Dimethyl-5- 6 -(9-(thiophen-3-yl)-3,9-diazaspiro[5.5]undec-3-yl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0352] 1 1 ,2 6 -Dimethyl-5- 6 -(9-(1-oxidothiophen-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0353] 5 6 -(9-(1,1-dioxidothiophene-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0354] 5 6 -(7-hydroxy-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0355] 5 6 -(7-methoxy-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0356] 5 6 -(7-fluoro-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0357] 1 1 ,2 6 -Dimethyl-5- 6-(3-(oxetane-3-yl)-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidinyl]-1'-yl)-1 1 H, 5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0358] 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(3,4)-quinolin-5(2,1)-benzo[d]imidazol-2(2,4)-pyridocycloundecan-3-one;

[0359] 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(8,7)-quinolin-5(2,1)-benzo[d]imidazol-2(2,4)-pyridocycloundecan-3-one;

[0360] 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(3,4)-pyridazin-2(2,4)-pyridocycloundecan-3-one;

[0361] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-3-one;

[0362] 5 6 -(9-(3,3-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0363] 5 6 -(9-(5-oxaspiro[2.5]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0364] 5 6 -(9-(3-fluorotetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0365] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2,3,5,6-tetramethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0366] 5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0367] 5 6 -(9-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1, 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0368] 1 1 , 2 6 -Dimethyl-5- 6 -(9-((2S)-2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0369] 1 1 , 2 6 -Dimethyl-5- 6 -(9-((2R)-2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0370] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0371] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(2-(methylsulfonyl)ethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one;

[0372] (R)-5 5-(3-(dimethylamino)pyrrolidin-1-yl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0373] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(3-((methylsulfonyl)methyl)azetidin-1-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0374] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(tetrahydrofuran-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0375] 5 5 -cyclopropyl-1 1 , 2 6 -dimethyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0376] 5 5 -(1,1-dioxotetrahydro-2H-thiopyran-4-yl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0377] 5 5 -(2-ethoxyethyl)-1 1 , 2 6 -dimethyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0378] 11-cyclopropyl-26-methyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0379] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(piperidin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0380] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(1-methylpiperidin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0381] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(1-(methylsulfonyl)piperidin-4-yl)-1 1H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0382] (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0383] (R)-1 1 ,2 6 ,7-trimethyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0384] (R)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0385] (R)-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0386] (7R)-1 1 ,2 6 ,7-trimethyl-5 6-(3-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0387] (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-5- 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-1 1 H,51H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0388] (R)-5 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0389] (R)-5 5 -Fluoro-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0390] (R)-5 5 -Fluoro-5 6 -(9-(4-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0391] (7R)-5 5 -Fluorine-1 1 ,2 6 ,7-trimethyl-5 6 -(3-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-1'-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0392] (R)-5 5 -Fluoro-5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0393] (R)-5 5 -Fluoro-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0394] (R)-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0395] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5-((2-(methylsulfonyl)ethyl)amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one;

[0396] (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0397] (R)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0398] (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0399] (R)-1 1 , 2 6 ,7-tris(methyl-d3)-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0400] 55 -(3-hydroxy-3-methylbutyl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0401] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0402] (R)-5 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0403] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecyl-3-one;

[0404] 5 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0405] (R)-26 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-(2-oxetane-3-ylamino)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0406] 1 1 , 2 6 ,5 5 -Trimethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0407] (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0408] (E)-1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 2 ,5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolidinecyclodecane-3-one;

[0409] (R)-1 1 ,2 6 ,7-trimethyl-5 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0410] (R)-55 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0411] (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0412] (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one;

[0413] 2 6 -methyl-5 5 -(Oxetane-3-ylamino)-5-(2-oxetane-3-ylamino)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0414] 2 6 -methyl-5 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0415] (R)-2 6 ,7-dimethyl-5 5-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0416] 5 6 -Fluorine-1 1 ,2 6 -dimethyl-55-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0417] 1 1 ,2 6 ,5 6 -Trimethyl-5 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0418] 1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 6 -(methylamino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0419] 1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 6 -(Oxetane-3-ylamino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0420] 2 6 -methyl-5 6-(3-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-1'-yl)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0421] 5 5 ,5 6 -Dimethoxy-2 6 -methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0422] 2 6 -methyl-5 3 ,5 6 ,5 7 ,5 8 -Tetrahydro-11-oxa-4-aza-5(2,3)-imidazo[4',5':4,5]benzo[1,2-b][1,4]oxazine-1(3,4),2(2,4)-bipyridocycloundecane-5- 7 ,3-diketone;

[0423] (7R)-2 6 ,7-dimethyl-5 6 -(3-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-1'-yl)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecane-3-one;

[0424] 2 6 -Methyl 5 6 -((3-methyl-3-azaspiro[5.5]undec-9-yl)amino)-5- ... 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0425] 2 6 ,5 5 ,5 8 -Trimethyl 5 5 ,5 6 ,5 7 ,5 8 -Tetrahydro-5- 1 H-11-oxa-4-aza-5(2,1)-imidazo[4,5-g]quinoxaline-1(3,4),2(2,4)-bipyridocycloundecan-3-one;

[0426] (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0427] 2 6 -methyl-5 5 ,5 6 -bis(methylamino)-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0428] (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H,5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocyclodecane-3-one;

[0429] 2 6 -methyl-5 5 H-11-oxa-4-aza-5(6,5)-[1,3]dioxa[4′,5′:4,5]benzo[1,2-d]imidazole-1(3,4),2(2,4)-dipyridocycloundeca-3-one;

[0430] 5 6 -((dimethyl(oxy)-λ 6 -aminosulfonyl imide)-2 6 -methyl-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecane-3-one;

[0431] 2 6 -methyl-5 6 ,5 7 -Dihydro-5 1H-11-oxa-4-aza-5(2,1)-[1,4]dioxy[2′,3′:4,5]benzo[1,2-d]imidazol-1(3,4),2(2,4)-dipyridocycloundecane-3-one;

[0432] (R)-5 5 -Amino-1 1 ,2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one;

[0433] (7R)-5 6 -(9-(4-methoxy-4-methylpentan-2-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecane-3-one;

[0434] 5 6 -(dimethylphosphoryl)-2 6 -methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundeca-3-one;

[0435] 5 6 -(ethylsulfonyl)-2- 6 -methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0436] (R)-5 6 -((dimethyl(oxy)-λ 6 Aminosulfonyl imide)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0437] (R)-2 6 ,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecan-3-one;

[0438] (R)-5 6 -((dimethyl(oxy)-λ 6 Sulfonamide)amino)-2 6 ,7-dimethyl-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecane-3-one;

[0439] (R)-2 6 ,7-dimethyl 5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecan-3-one;

[0440] (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocyclohexen-3-one;

[0441] (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocyclohexen-3-one;

[0442] (R)-2 6 ,7-dimethyl-5 5 -(thiophen-3-ylamino)-5-(thiophen-3-ylamino)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0443] (R)-5 5 -(isoxazol-4-ylamino)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0444] (R)-5 5 -((2-methoxyethyl)amino)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0445] (R)-5 5 -((1,1-dioxidithiophen-3-yl)amino)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0446] (R)-2 6 ,7-dimethyl-5 5 -((1-thiophen-3-yl)amino)-5- ... 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0447] (R)-(2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 5 -yl) urethane;

[0448] (R)-N-(2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 5 -yl)methanesulfonamide;

[0449] (R)-5 5 -((1,1-dioxidithiophen-3-yl)amino)-2 6 ,7-dimethyl-5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0450] (R)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-(2-oxetane-3-ylamino)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(3,4)-pyridazin-2(2,4)-pyridocycloundecan-3-one;

[0451] (R)-N-(2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 5 -yl)-1-fluoromethanesulfonamide;

[0452] (R)-N-(2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 5 -yl)-1,1,1-trifluoromethanesulfonamide;

[0453] (R)-2 6 ,7-dimethyl-5 5 -(((S)-tetrahydrofuran-3-yl)amino)-5- ... 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0454] (R)-2 6 ,7-dimethyl-5 5 -(((R)-tetrahydrofuran-3-yl)amino)-5- ... 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0455] (R)-2 6 ,5 6 ,7-trimethyl-5 5 -(Oxetane-3-ylamino)-5-(2-oxetane-3-ylamino)- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0456] (R)-5 6 -Fluorine-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0457] (R)-5 6 -Chloro-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0458] (R)-5 6 -Methoxy-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0459] (R)-5 6 -(2-(dimethylamino)ethoxy)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridylcycloundecan-3-one;

[0460] (R)-5 6 -(2-methoxyethoxy)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0461] (R)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-5,6-((1-oxotetrahydro-1λ 6 -thiophen-1-ylidene)amino)-5- 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-dipyridocycloundecan-3-one;

[0462] (R)-N-(2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl)methanesulfonamide;

[0463] (R)-N-(2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl)ethanesulfonamide;

[0464] (R)-N-(2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl)-1-fluoromethanesulfonamide; or

[0465] (R)-2 6 ,7-dimethyl-5 6 -((4-methylpiperazin-1-yl)methyl)-5-(4-methylpiperazin-1-yl)methyl)- 5 -(Oxetane-3-ylamino)-5-nitropropane 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecan-3-one.

[0466] (R)-2 6 ,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0467] (R)-2 6 ,7-dimethyl 5 6-(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0468] (R)-7-Methyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0469] (R)-2 6 -Chloro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0470] (R)-2 6 -methoxy-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0471] (R)-2 6 -ethyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0472] (R)-2 6 -isopropyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0473] (R)-1 5 -Fluorine-2 6,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0474] (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 5 -Fluorine-2 6 ,7-dimethyl 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0475] (R)-1 5 -Fluorine-2 6 ,7-dimethyl 5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0476] (R)-1 4 ,1 5 -Difluoro-2 6 ,7-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0477] (R)-7-Methyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-5-( 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0478] (R)-2 6 -cyclopropyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0479] (R)-2 6 -ethynyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0480] (R)-1 5 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -carbonitrile;

[0481] (R)-1 4 ,1 5 -difluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0482] (R)-1 4 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -carbonitrile;

[0483] (R)-7-Methyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0484] (R)-56 -(9-ethyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0485] (R)-5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0486] (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0487] (7R)-7-methyl-3-oxo-5- 6 -(9-(tetrahydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0488] (R)-7-methyl-3-oxo-5- 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0489] (7R)-5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-26 -nitrile;

[0490] (7R)-5 6 -(9-(2-oxabicyclo[2.2.1]heptane-5-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0491] (R)-(2-(9-(2 6 -cyano-7-methyl-3-oxo-51H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)ethyl)carbamic acid methyl ester;

[0492] (R)-3-(9-(2 6 -cyano-7-methyl-3-oxo-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-dihydro-1-nitro-2-nitro-1 ... 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)-N,N-dimethylpropionamide;

[0493] (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0494] (R)-5 6 -(9-(3-cyclopropyloxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0495] (R)-7-Methyl-5- 6 -(9-(3-(methylsulfonyl)propyl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5-1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0496] (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0497] (R)-5 6 -(9-(2-(dimethylamino)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0498] (7R)-7-Methyl 5- 6 -(9-(2-methyloxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0499] (R)-5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0500] (R)-5 6 -(9-(3,3-difluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0501] (R)-7-methyl-3-oxo-5-6 -(9-(2-(trifluoromethoxy)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0502] (R)-5 6 -(9-(cyanomethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0503] 9,9-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile;

[0504] (R)-5 6 -(9-(3-(azetidin-1-yl)-3-oxopropyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -Chloro-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0505] (R)-2 6 -Chloro-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0506] (R)-2 6 -Chloro-7-methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0507] (R)-2 6 -Chloro-7-methyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0508] (7R)-2 6 -Chloro-5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0509] (R)-2 6 -Chloro-1 5 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0510] (R)-2 6 -Chloro-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0511] 2 6 -Chloro-9,9-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0512] (R)-2 6 -Chloro-1 4 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0513] (R)-2 6 -Chloro-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0514] (R)-2 6 -Chloro-5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one;

[0515] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0516] (R)-1 5 -Fluorine-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0517] (R)-1 4 -Fluorine-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0518] (R)-2 6 -Chloro-7-methyl-3-oxo-5 1H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0519] (R)-2 6 -cyano-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0520] (R)-2 6 -methoxy-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0521] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 - 4-methylpiperazine-1-carboxylate;

[0522] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl 9-methyl-3,9-diazaspiro[5.5]undecane-3-carboxylate;

[0523] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -amino (2-(dimethylamino)ethyl) carbamate;

[0524] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole6 -yl (2-methyl-2-azabicyclo [2.2.1] heptane-5-yl) carbamate;

[0525] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (2-methyloctahydrocyclopenta[c]pyrrol-5-yl) carbamate;

[0526] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (2-methoxyethyl) carbamate;

[0527] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpyrrolidin-3-yl) carbamate;

[0528] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl(tetrahydrofuran-3-yl)carbamate;

[0529] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecanepentaenoic acid-5-(2,1)-benzo[d]imidazole 6 -Oxetane-3-ylcarbamate;

[0530] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylazetidin-3-yl) carbamate;

[0531] (R)-2 6 ,5 5 ,7-trimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0532] (R)-5 5 -Fluorine-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0533] (R)-5 5 -Chloro-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0534] (R)-5 5 -Methoxy-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0535] (R)-5 5 -Cyano-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0536] (R)-5 5 -(dimethylamino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole6 -yl (1-methylpiperidin-4-yl) carbamate;

[0537] (R)-5 5 -((2-(dimethylamino)ethyl)(methyl)amino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0538] (R)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5- 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0539] (R)-5 5 -((dimethyl(oxo)-l 6 -sulfonamido)amino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0540] (R)-2 6 -Chloro-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-3-yl) carbamate;

[0541] (R)-2 6 -cyano-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl (1-methylpiperidin-3-yl) carbamate;

[0542] (R)-2 6 ,7-dimethyl-3-oxo-5 1H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 7 -yl (1-methylpiperidin-4-yl) carbamate;

[0543] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-benzo[d]imidazole 5 -yl (1-methylpiperidin-4-yl) carbamate;

[0544] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0545] (R)-2 6 ,5 5 ,7-trimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0546] (R)-5 5 -Fluorine-2 6 ,7-dimethyl-3-oxo-51H-11-oxo-4-aza-5(2,1)-benzo[d]imidazol-1(3,4),2(2,4)-dipyridocycloundecane-56-yl(1-methylpiperidin-4-yl)carbamate;

[0547] (R)-5 5 -Chloro-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0548] (R)-5 5 -Methoxy-2 6 ,7-dimethyl-3-oxo-5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0549] (R)-5 5 -Cyano-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0550] (R)-5 5 -(dimethylamino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0551] (R)-5 5 -((2-(dimethylamino)ethyl)(methyl)amino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0552] (R)-2 6 ,7-dimethyl-5 5 -(Oxetane-3-ylamino)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-4-yl) carbamate;

[0553] (R)-5 5 -((dimethyl(oxo)-l 6 -sulfanyl)amino)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6-yl (1-methylpiperidin-4-yl) carbamate;

[0554] (R)-2 6 -Chloro-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-3-yl) carbamate;

[0555] (R)-2 6 -cyano-7-methyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpiperidin-3-yl) carbamate;

[0556] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl 9-methyl-3,9-diazaspiro[5.5]undecane-3-carboxylate;

[0557] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -amino (2-(dimethylamino)ethyl) carbamate;

[0558] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (2-methoxyethyl) carbamate;

[0559] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylpyrrolidin-3-yl) carbamate;

[0560] (R)-26 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl(tetrahydrofuran-3-yl)carbamate;

[0561] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -Oxetane-3-ylcarbamate;

[0562] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -yl (1-methylazetidin-3-yl) carbamate;

[0563] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 7 -yl (1-methylpiperidin-4-yl) carbamate;

[0564] (R)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 5 -yl (1-methylpiperidin-4-yl) carbamate; or

[0565] (7R)-N-(2,6-dioxopiperidin-3-yl)-2 6 ,7-dimethyl-3-oxo-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecane-5-ol 6 -formamide.

[0566] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of formula (I), or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, and at least one pharmaceutically acceptable excipient.

[0567] The present invention also provides the use of the above-mentioned compound and / or pharmaceutical composition in the preparation of an anti-tumor drug. In certain embodiments, the anti-tumor drug is used for the following conditions: head and neck cancer, melanoma, bladder cancer, esophageal cancer, anaplastic large cell lymphoma, renal cell carcinoma, breast cancer, colorectal cancer, ovarian cancer, cervical cancer, pancreatic cancer, glioma, glioblastoma, prostate cancer, leukemia, lymphoma, non-Hodgkin's lymphoma, gastric cancer, lung cancer, hepatocellular carcinoma, gastrointestinal stromal tumor, thyroid cancer, bile duct cancer, endometrial cancer, multiple myeloma, or mesothelioma.

[0568] In certain embodiments, the tumor is a malignant tumor carrying an EGFR gene mutation; preferably, the EGFR gene mutation is selected from one or more of: EGFR Del19 gene mutation, EGFR L858R gene mutation, EGFR T790M gene mutation and EGFR C797S gene mutation.

[0569] The present invention also provides a method for treating tumors in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the above-mentioned compound and / or pharmaceutical composition, wherein the patient is preferably a mammal, and the mammal is preferably a human.

[0570] In certain embodiments, the administration during treatment comprises oral, mucosal, sublingual, ocular, topical, parenteral, rectal, intracisternal, vaginal, peritoneal, bladder, or nasal administration.

[0571] In some embodiments, the tumor comprises head and neck cancer, melanoma, bladder cancer, esophageal cancer, anaplastic large cell lymphoma, renal cell carcinoma, breast cancer, colorectal cancer, ovarian cancer, cervical cancer, pancreatic cancer, glioma, glioblastoma, prostate cancer, leukemia, lymphoma, non-Hodgkin lymphoma, gastric cancer, lung cancer, hepatocellular carcinoma, gastrointestinal stromal tumor, thyroid cancer, bile duct cancer, endometrial cancer, multiple myeloma, or mesothelioma.

[0572] In certain embodiments, the tumor is a malignant tumor carrying an EGFR gene mutation; preferably, the EGFR gene mutation is selected from one or more of: EGFR Del19 gene mutation, EGFR L858R gene mutation, EGFR T790M gene mutation and EGFR C797S gene mutation.

[0573] Definition and Description

[0574] General chemical terms used in the above structural formulas have their usual meanings.

[0575] For example, unless otherwise indicated, the terms "halo" and "halogen" as used herein refer to fluorine, chlorine, bromine or iodine. Preferred halogen groups include fluorine, chlorine and bromine.

[0576] In the present invention, unless otherwise specified, the term "alkyl" includes a linear or branched monovalent saturated hydrocarbon group, preferably a C 1-6 Alkyl, more preferably C 1-3 Alkyl. The alkyl groups used herein may be optionally substituted with one or more substituents. Non-limiting examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, n-hexyl, 2-hexyl, 2-methylpentyl, and the like. Similarly, “C 1-6 "C" in "alkyl" 1-6 ” refers to a group containing 1, 2, 3, 4, 5 or 6 carbon atoms in a straight or branched chain.

[0577] The terms "alkenyl" and "alkynyl" include straight or branched chain alkenyl and alkynyl groups. 2-6 Alkenyl" and "C 2-6 "Alkynyl" refers to an alkenyl or alkynyl group containing 2, 3, 4, 5 or 6 carbon atoms arranged in a straight chain or branched form.

[0578] The term "alkoxy" refers to the oxygen ether form of the aforementioned straight-chain or branched alkyl groups.

[0579] The term "haloalkyl" refers to the aforementioned "alkyl" substituted by one or more halogens.

[0580] In the present invention, "a", "an", "the", "at least one" and "one or more" are used interchangeably. Thus, for example, a composition comprising "a" pharmaceutically acceptable excipient can be interpreted to mean that the composition includes "one or more" pharmaceutically acceptable excipients.

[0581] The term "aryl" in the present invention, unless otherwise specified, refers to an unsubstituted or substituted monocyclic, fused or condensed aromatic group containing carbon atoms, preferably C 6-14 Aryl, the C 6-14 Aryl is more preferably C 6-10 Examples of these aromatic rings include, but are not limited to, phenyl and naphthyl.

[0582] The term "heteroaryl" refers to a monocyclic or polycyclic (e.g., fused bicyclic) aromatic heterocycle having at least one heteroatom ring member (e.g., 1 to 4 heteroatoms, or preferably 1 to 3 heteroatoms), wherein the heteroatoms are selected from N, O, and / or S. The nitrogen or sulfur heteroatom may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heteroaryl group may be attached to any heteroatom or carbon atom to produce a stable structure. The heteroaryl group is preferably a 5-14 membered heteroaryl group, and the 5-14 membered heteroaryl group is further preferably a 5-10 membered heteroaryl group or a 5-6 membered heteroaryl group. Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, triazolyl, pyridinyl, pyridazinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, benzoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyladeninyl, quinolinyl, or isoquinolinyl.

[0583] The term "carbocyclyl" refers to a saturated or unsaturated cyclic group that is not aromatic. Depending on its degree of saturation, it may include "cycloalkyl", "cycloalkenyl" or "cycloalkynyl". Monocyclic carbocyclyl groups include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane or cyclohexene and the like; polycyclic carbocyclyl groups include spirocyclic, fused ring, bridged ring carbocyclyl groups. The carbocyclyl is preferably C 3-14 Carbocyclic group, the C 3-14 The carbocyclic group is more preferably C 3-8 Carbocyclic group, the C 3-8 The carbocyclic group is more preferably C 3-6 Carbocyclic group, the C 3-8 The carbocyclic group is more preferably C 5-6 Carbocyclic group.

[0584] The term "cycloalkyl" refers to saturated monocyclic and polycyclic ring systems containing only carbon atoms in the ring and may be optionally substituted with one or more substituents. "Cycloalkyl" may have ring systems including bridged rings, fused rings, and spiro rings. Non-limiting examples of cycloalkyl include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.4]octyl, bicyclo[2.2.1]heptane, and the like. The cycloalkyl is preferably C 3-14 Cycloalkyl, the C 3-14 The cycloalkyl group is more preferably C 3-8 Cycloalkyl, the C 3-8 The cycloalkyl group is more preferably C 3-6 Cycloalkyl, the C 3-8 The cycloalkyl group is more preferably C 5-6 Cycloalkyl.

[0585] The term "heterocyclyl" in the present invention, unless otherwise indicated, refers to unsubstituted or substituted monocyclic and polycyclic ring systems consisting of carbon atoms and 1-3 heteroatoms selected from N, O or S, and includes saturated or unsaturated ring systems and polycyclic ring systems with unsaturated and / or aromatic moieties. The nitrogen or sulfur heteroatom can be selectively oxidized, and the nitrogen heteroatom can be selectively quaternized. The heterocyclyl can be attached to any heteroatom or carbon atom to form a stable structure. It should be understood that the polycyclic heterocycloalkyl group can have a ring system including fused rings, bridged rings and spirocycles. The heterocyclyl is preferably a 3-14 membered heterocyclyl, and the 3-14 membered heterocyclyl is further preferably a 3-8 membered heterocyclyl or a 5-10 membered heterocyclyl, and the 3-8 membered heterocyclyl is further preferably a 3-6 membered heterocyclyl, and the 3-6 membered heterocyclyl is further preferably a 5-6 membered heterocyclyl. The heterocycloalkyl group used herein may optionally be substituted with one or more substituents. Examples of such heterocyclic groups include, but are not limited to, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, tetrahydrofuranyl, dioxolanyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinylsulfoxide, thiomorpholinylsulfone, and tetrahydrooxadiazolyl.

[0586] However, in no case will heterocyclyls and carbocyclyls intersect or include each other. Thus, according to the above definition, if at least one all-carbocycle is fused with a heterocyclyl to form a bi-, poly- or spiro-ring, it will still be defined as a heterocyclyl.

[0587] Additionally, if a heteroaryl group is fused with a heterocyclyl group to form a bi-, poly-, or spiro-ring, it will be defined as a heterocyclyl group rather than a heteroaryl group.

[0588] The term "substituted" means that one or more hydrogen atoms in a group are replaced by the same or different substituents. Typical substituents include but are not limited to halogen (F, Cl, Br or I), C 1-8 Alkyl, C 3-12 Cycloalkyl, -OR 1 、-SR 1 , =O, =S, -C(O)R 1 、-C(S)R 1 、=NR 1 、-C(O)OR 1 、-C(S)OR 1 、-NR 1 R 2 、-C(O)NR 1 R 2 , cyano, nitro, -S(O)2R 1 、-OS(O2)OR 1、-OS(O)2R 1 、-OP(O)(OR 1 )(OR 2 ); where R 1 and R 2 Independently selected from -H, C 1-6 Alkyl, C 1-6 In some embodiments, the substituents are independently selected from the group consisting of -F, -Cl, -Br, -I, -OH, trifluoromethoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, -SCH 3 , -SC 2 H 5 , formaldehyde, -C(OCH 3 ), cyano, nitro, -CF 3 , -OCF 3 , amino, dimethylamino, methylthio, sulfonyl, and acetyl.

[0589] The term "pharmaceutically acceptable salt" refers to a salt prepared from a pharmaceutically acceptable base or acid. When the compound provided by the present invention is an acid, its corresponding salt can be conveniently prepared from a pharmaceutically acceptable base, including inorganic bases and organic bases.

[0590] As used herein, "deuterated" refers to a compound or chemical group formed when some or all of the hydrogen atoms in its structure are replaced by its isotope, deuterium. Any position specifically designated as "D" or "deuterium" is understood to have a deuterium enrichment of 50%, 80%, 90%, 95%, 98%, or 99%. "Deuterium enrichment" is a molar percentage determined by dividing the number of deuterium-containing compounds at the designated position by the total number of all compounds. When a position is designated as "H" or "hydrogen," hydrogen is present at its natural abundance at that position. When a position is silent regarding the presence of hydrogen or deuterium, hydrogen is present at its natural abundance at that position. A specific alternative embodiment relates to compounds of the present disclosure having a deuterium enrichment of at least 5%, 10%, 25%, 50%, 80%, 90%, 95%, 98%, or 99% at one or more positions not specifically designated as "D" or "deuterium." In some embodiments, one or more hydrogen atoms of any compound described herein can be replaced with deuterium to provide the corresponding labeled or enriched compound.

[0591] The "deuterated C 1-6 "Alkyl" refers to "C 1-6 "Deuterated methyl" refers to a group in which the hydrogen atoms in the methyl structure are partially or completely replaced by their isotopes deuterium; "deuterated methyl" refers to a group in which the hydrogen atoms in the methyl structure are partially or completely replaced by their isotopes deuterium. CD3 is a group in which the hydrogen atoms in the methyl structure are completely replaced by their isotopes deuterium. The deuterated C 1-6 The alkyl group is preferably a deuterated C 1-3 Alkyl; the deuterated C 1-3 The alkyl group is preferably a deuterated methyl group.

[0592] Since the compound represented by formula (I) is to be used as a medicine, it is preferably used with a certain purity, for example, at least 60% purity, more preferably at least 75% purity, and particularly preferably at least 98% purity (% is weight ratio).

[0593] Prodrugs of the compounds of the present invention are included within the scope of the present invention. Generally, the prodrug refers to a functional derivative that is easily converted into the desired compound in vivo. For example, any pharmaceutically acceptable salt, ester, salt of an ester, or other derivative of the compounds of the present invention, which, upon administration to a recipient, can directly or indirectly provide the compounds of the present invention or their pharmaceutically active metabolites or residues. Particularly preferred derivatives or prodrugs are those that can increase the bioavailability of the compounds of the present invention when administered to a patient (e.g., by making orally administered compounds more readily absorbed into the blood), or those that promote the delivery of the parent compound to biological organs or sites of action (e.g., the brain or lymphatic system). Therefore, the term "administration" in the treatment methods provided herein refers to the administration of the compounds of the present invention that can treat various diseases, or, although not explicitly disclosed, can be converted into the compounds of the present invention in vivo upon administration to a subject. Conventional methods for selecting and preparing suitable prodrug derivatives are described in books such as "Design of Prodrugs" (ed. H. Bundgaard, Elsevier, 1985).

[0594] Obviously, the definition of any substituent or variable at a particular position in a molecule is independent of the definition of any other position in the molecule. It is readily understood that one skilled in the art can select substituents or substitution patterns for the compounds of the present invention using existing techniques and the methods described herein to obtain chemically stable and readily synthesized compounds.

[0595] The compounds of the present invention may contain one or more asymmetric centers and may thus produce diastereomers and optical isomers. The present invention includes all possible diastereomers and racemic mixtures thereof, their substantially pure resolved enantiomers, all possible geometric isomers and pharmaceutically acceptable salts thereof.

[0596] The above formula (I) does not precisely define the stereostructure of a particular position of the compound. The present invention includes all stereoisomers of the compound represented by formula (I) and pharmaceutically acceptable salts thereof. Furthermore, mixtures of stereoisomers and isolated specific stereoisomers are also included in the present invention. During the synthetic process for preparing such compounds, or using racemization or epimerization processes known to those skilled in the art, the resulting product may be a mixture of stereoisomers.

[0597] When the compound represented by formula (I) exists in tautomers, unless otherwise stated, the present invention includes any possible tautomers and pharmaceutically acceptable salts thereof, and mixtures thereof.

[0598] When the compound represented by formula (I) and its pharmaceutically acceptable salt exist in solvates or polymorphs, the present invention includes any possible solvates and polymorphs. The type of solvent forming the solvate is not particularly limited, as long as the solvent is pharmaceutically acceptable.

[0599] The term "composition," as used herein, is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product produced, directly or indirectly, from combination of the specified ingredients in the specified amounts. Thus, pharmaceutical compositions containing a compound of the invention as an active ingredient, as well as methods for preparing the compounds of the invention, are also part of this invention.

[0600] In addition, some crystalline forms of the compound can exist as polymorphs, and such polymorphs are included in the present invention. In addition, some compounds can form solvates with water (i.e. hydrates) or common organic solvents, and such solvates also fall within the scope of the present invention.

[0601] The pharmaceutical composition provided by the present invention includes a compound shown in formula (I) (or a pharmaceutically acceptable salt thereof) as an active ingredient, a pharmaceutically acceptable excipient and other optional therapeutic components or adjuvants. Although in any given case, the most suitable active ingredient administration method depends on the specific subject, subject property and severity of the disease to be administered, the pharmaceutical composition of the present invention includes a pharmaceutical composition suitable for oral, rectal, local and parenteral (including subcutaneous administration, intramuscular injection, intravenous administration) administration. The pharmaceutical composition of the present invention can be conveniently prepared in any unit dosage form known in the art and any preparation method known in the pharmaceutical field.

[0602] The pharmaceutical compositions of the present invention can be prepared by any pharmaceutical method. Generally, such methods include the step of combining the active ingredient with a carrier comprising one or more essential ingredients. Typically, the pharmaceutical compositions are prepared by uniformly and intimately mixing the active ingredient with a liquid carrier, a finely divided solid carrier, or a mixture thereof. Furthermore, the product can be readily prepared to a desired appearance.

[0603] Therefore, the pharmaceutical composition of the present invention comprises a pharmaceutically acceptable carrier and a compound represented by formula (I) or its stereoisomers, tautomers, polymorphs, solvates, pharmaceutically acceptable salts, or prodrugs. Combinations of the compound represented by formula (I) or its pharmaceutically acceptable salts with one or more other therapeutically active compounds are also included in the pharmaceutical composition of the present invention.

[0604] The drug carrier used in the present invention can be, for example, a solid carrier, a liquid carrier or a gaseous carrier. DETAILED DESCRIPTION

[0605] To make the above content clearer and more specific, the present invention will further illustrate the technical solutions of the present invention with the following examples. The following examples are only used to illustrate the specific embodiments of the present invention so that those skilled in the art can understand the present invention, but are not intended to limit the scope of protection of the present invention. In the specific embodiments of the present invention, technical means or methods not specifically described are conventional technical means or methods in the art.

[0606] Unless otherwise indicated, all parts and percentages herein are by weight and all temperatures are in degrees Celsius.

[0607] The following abbreviations are used in the examples: (Boc)2O: di-tert-butyl dicarbonate; BrettPhos Pd G3: methanesulfonic acid (2-dicyclohexylphosphino)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II); Pd(dppf)Cl2: [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium; Cs2CO3: cesium carbonate; MsCl: methanesulfonyl chloride; DIEA / DIPEA: N,N-diisopropylethylamine; TEA: triethylamine; DMF: N,N-dimethylformamide; DCM: dichloromethane; EA / EtOAc: ethyl acetate; EtOH: ethanol; CNBr: cyanogen bromide HATU: O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; TFA: trifluoroacetic acid; KI: potassium iodide; LC-MS or LCMS: liquid chromatography-mass spectrometry; LiAlH4: lithium aluminum hydride; Na2CO3: sodium carbonate; NaH: sodium hydride; K2CO3: potassium carbonate; LiOH: lithium hydroxide; STAB: sodium triacetoxyborohydride; Pd / C: palladium on carbon; Raney Ni: Raney nickel; BINAP: 1,1'-binaphthyl-2,2'-bis(diphenylphosphine); DPPA: diphenylphosphoryl azide; LiHDMS: lithium bis(trimethylsilylamide)amide Pd2(dba)3: tris(dibenzylideneacetone)dipalladium; t-BuONa: sodium tert-butoxide; PE: petroleum ether; Xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; Prep-HPLC: high performance liquid chromatography; PLC: preparative liquid chromatography; TLC: thin layer chromatography; AcOH: glacial acetic acid; THF: tetrahydrofuran; Xphos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl; Fe: iron powder; CMBP: cyanomethylenetri-n-butylphosphine; TBAF: tetrabutylammonium fluoride; DMAP: 4-dimethylaminopyridine.

[0608] The raw materials and reagents used in the examples can be obtained from commercial sources or prepared by conventional methods in the art.

[0609] Example 2 Synthesis of Compound A02

[0610] 1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,7-diazaspiro[3.5]nonan-7-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridinyl-1(4,5)-pyrazolocycloundecyl-3-one

[0611] Step 1: Synthesis of compound A02-1

[0612] In a 500 mL single-necked bottle, methyl 2-chloro-6-methylisonicotinate (10 g, 53.88 mmol), 5-hydroxy-1-methylpyrazole (6.34 g, 64.65 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (4.4 g, 5.39 mmol), sodium carbonate (11.42 g, 107.75 mmol), and anisole (100 mL) were mixed uniformly and reacted at 130°C for 12 h under nitrogen. The reaction mixture was cooled to room temperature after TLC monitoring for the disappearance of the starting material and then directly purified by column chromatography (PE for 10 min, PE / EA 0-50% for 10 min, and DCM / MeOH 0-3% for 15 min) to afford compound A02-1 (8.00 g, 32.35 mmol, 60% yield). MS: 248.10 [M+H] +

[0613] Step 2: Synthesis of compound A02-2

[0614] In a reaction flask, 4-bromo-2-fluoro-1-nitrobenzene (1.00 g, 4.55 mmol), 5-aminopentan-1-ol (0.52 g, 5.00 mmol), potassium carbonate (1.88 g, 13.64 mmol), and DMF (10 mL) were mixed thoroughly and stirred at room temperature overnight. The reaction mixture was poured into 50 mL of ice water and filtered, rinsed with water (3 x 15 mL). The filter cake was dried under vacuum to obtain the product, compound A02-2 (1.2 g, yield: 94%). MS: 303.03, 305.03 [M+H] +

[0615] Step 3: Synthesis of compound A02-3

[0616] A02-2 (1.20 g, 3.96 mmol), triethylamine (1.10 mL, 7.92 mmol), and DCM (20 mL) were added to a reaction flask. MsCl (0.54 g, 4.75 mmol) was added under ice-cooling. The reaction was allowed to react at room temperature for 2 h. The reaction was monitored for completion by LCMS. The product was then dried and purified by column chromatography using PE / EA = 1 / 1 to obtain the product compound A02-3 (1.40 g, yield: 92%). MS: 381.00, 383.01 [M+H] +

[0617] Step 4: Synthesis of Compound A02-4

[0618] In a 100 mL single-necked bottle, compound A02-3 (0.62 g, 1.62 mmol), A02-1 (0.40 g, 1.62 mmol), potassium carbonate (0.45 g, 3.24 mmol), and DMF (10 mL) were mixed and reacted at 60°C for 6 h. The reaction was monitored by LCMS until complete. 30 mL of ethyl acetate was added, and the mixture was washed with 3 x 20 mL of saturated brine. The organic phase was dried and purified by column chromatography using DCM / EA = 3 / 1 to obtain compound A02-4 (0.80 g, yield: 93%). MS: 532.11, 534.11 [M+H] +

[0619] Step 5: Synthesis of Compound A02-5

[0620] Compound A02-4 (0.80 g, 1.50 mmol), iron powder (0.42 g, 7.51 mmol), ammonium chloride (0.40 g, 7.51 mmol), ethanol (8 mL), and H2O (4 mL) were mixed and reacted at 60°C for 1 h. The reaction was complete after LCMS monitoring. The mixture was filtered, cooled, and dried by spin chromatography. The product, compound A02-5 (0.60 g, yield: 79%), was obtained by column chromatography using DCM / MeOH = 10 / 1. MS: 502.14, 504.14 [M+H] +

[0621] Step 6: Synthesis of Compound A02-6

[0622] Compound A02-5 (600 mg, 1.19 mmol), cyanogen bromide (139 mg, 1.31 mmol), methanol (5 mL), and water (1 mL) were mixed and reacted at 70°C for 1 h. The reaction was monitored by LCMS. The pH was adjusted to 8, and the product was extracted with 3 x 50 mL of DCM and dried to give the product compound A02-6 (600 mg, yield: 95%). MS: 527.13, 529.13 [M+H] +

[0623] Step 7: Synthesis of Compound A02-7

[0624] Compound A02-6 (600 mg, 1.14 mmol), NaOH (227 mg, 5.69 mmol), methanol (2 mL), and water (2 mL) were mixed and reacted at room temperature for 1 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 7, and the mixture was extracted with 3 x 50 mL DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give compound A02-7 (560 mg, yield: 95%). MS: 513.12, 515.12 [M+H] +

[0625] Step 8: Synthesis of Compound A02-8

[0626] Compound A02-7 (3.9 g, 7.60 mmol), DIEA (2.51 mL, 15.19 mmol), and DCM (100 mL) were mixed uniformly. HATU (1.96 g, 15.19 mmol) was added under ice-cooling. The mixture was allowed to react at 10°C for 30 min. LCMS monitored the reaction completion. 100 mL of water was added to quench the reaction, and the mixture was extracted with 3 x 50 mL of DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and slurried in 50 mL of DCM to obtain compound A02-8 (2.50 g, yield: 66.4%). MS: 495.11, 497.11 [M+H] +

[0627] Step 9: Synthesis of Compound A02

[0628] Compound A02-8 (30 mg, 0.06 mmol), 2-methyl-2,7-diazaspiro[3.5]nonane (17 mg, 0.12 mmol), methanesulfonic acid (2-dicyclohexylphosphine)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium (II) (11 mg, 0.01 mmol), dioxane (1 mL), LiHDMS (0.3 mL, 0.30 mmol, 1 M) were mixed evenly, protected by nitrogen, reacted at 60 ° C for 30 min, and directly prepared by Prep-HPLC. The chromatographic column was luna C18, 30*250mm, mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile from 17% to 50%, 20 mins), to obtain the product compound A02 (10.3 mg, 0.02 mmol, yield: 30.6%). MS: 555.31 [M+H] +

[0629] Example 3 Synthesis of Compound A03

[0630] 5 7-(2-acryloyl-2,7-diazaspiro[3.5]non-7-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0631] Step 1: Synthesis of compound A03-1

[0632] The synthesis method of compound A03-1 is the same as that of compound A02-2, except that 4-bromo-2-fluoro-1-nitrobenzene is replaced with 2-fluoro-3-bromonitrobenzene. MS of compound A03-1: 303.03, 305.03 [M+H] +

[0633] Step 2: Synthesis of compound A03-2

[0634] The synthesis method of compound A03-2 is the same as that of compound A02-3, except that compound A02-2 is replaced by compound A03-1. MS of compound A03-2: 381.00, 383.01 [M+H] +

[0635] Step 3: Synthesis of compound A03-3

[0636] The synthesis method of compound A03-3 is the same as that of compound A02-4, except that compound A02-3 is replaced by compound A03-2. MS of compound A03-3: 532.11, 534.11 [M+H] +

[0637] Step 4: Synthesis of Compound A03-4

[0638] A03-3 (0.70 g, 1.31 mmol), platinum dioxide (0.15 g, 0.66 mmol), and ethyl acetate (10 mL) were mixed evenly, hydrogen was replaced three times, and the mixture was reacted at room temperature for 1 h. The mixture was filtered and dried by column chromatography using PE / EA = 1 / 1 to obtain the product compound A03-4 (0.40 g, 60.5%). MS: 502.14, 504.14 [M+H] +

[0639] Step 5: Synthesis of Compound A03-5

[0640] The synthesis method of compound A03-5 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A03-4. MS of compound A03-5: 527.13, 529.13 [M+H] +

[0641] Step 6: Synthesis of Compound A03-6

[0642] The synthesis method of compound A03-6 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A03-5. MS of compound A03-6: 513.12, 515.12 [M+H] +

[0643] Step 7: Synthesis of Compound A03-7

[0644] The synthesis method of compound A03-7 is the same as that of compound A02-8, except that compound A02-7 is replaced by compound A03-6. MS of compound A03-7: 495.11, 497.11 [M+H] +

[0645] Step 8: Synthesis of Compound A03-9

[0646] Compound A03-7 (100 mg, 0.20 mmol), compound A03-8 (68 mg, 0.30 mmol), Pd 2( dba)3 (37 mg, 0.04 mmol), xantphos (12 mg, 0.02 mmol), sodium tert-butoxide (78 mg, 0.81 mmol), and dioxane (5 mL) were mixed uniformly and reacted at 100°C for 8 h under nitrogen atmosphere. The reaction was monitored for completion by LCMS. Reverse phase preparative chromatography (mobile phase A: 0.05% FA, water; mobile phase B: ACN) with a gradient of 0-75% B over 20 min afforded the product, compound A03-9 (60 mg, 0.09 mmol, 46.4% yield). MS: 641.35 [M+H] +

[0647] Step 9: Synthesis of Compound A03-10

[0648] Compound A03-9 (60 mg, 0.09 mmol) was dissolved in DCM (5 mL), trifluoroacetic acid (2 mL) was added under ice-cooling, and the mixture was allowed to react at room temperature for 1 h. LCMS monitored the reaction completion, and the product was directly dried and used in the next step. MS of compound A03-10: 541.30 [M+H] +

[0649] Step 11: Synthesis of Compound A03

[0650] Compound A03-10 (40 mg, 0.07 mmol) and DIEA (0.06 mL, 0.37 mmol) were dissolved in DCM (5 mL). Acryloyl chloride (7 mg, 0.08 mmol) was added under ice-cooling. The reaction was monitored for completion by LCMS. Prep-HPLC was performed using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to obtain compound A03 (11 mg, 23% yield). MS: 595.31 [M+H] +

[0651] Example 4 Synthesis of Compound A04

[0652] 1 1 , 2 6 -Dimethyl-5- 6 -(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0653] Step 1: Synthesis of Compound A04

[0654] Compound A02-8 (99 mg, 0.2 mmol) and compound A04-1 (66.9 mg, 0.3 mmol) were added to the reaction flask, and solvent dioxane (1.2 mL) and water (0.3 mL) were added. Then, potassium carbonate (82.8 mg, 0.6 mmol) and Pd(dppf)Cl2 (15 mg, 0.02 mmol) were added. The atmosphere was replaced with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. After the disappearance of the starting material, heating was stopped, and the sample was mixed with silica gel and passed through the column. The eluent was changed from pure PE to pure EA, and the crude product was concentrated. Prep-HPLC was performed on a Luna C18 column, 30*250 mm, and the mobile phase was (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile was increased from 17% to 50% in 20 min). The preparative solution was rotary evaporated to remove the organic solvent, and lyophilized in a freeze dryer to obtain 30 mg of the product (95% purity, 29% yield). MS: 512.27 [M+H] + .

[0655] Example 7 Synthesis of Compound A07

[0656] 1 1 , 2 6 -Dimethyl-5- 6 -((1-methylpiperidin-4-yl)thio)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0657] Step 1: Synthesis of compound A07-2

[0658] Compound A02-8 (150 mg, 0.30 mmol), compound A07-1 (79 mg, 0.36 mmol), Pd 2( dba)3 (28 mg, 0.03 mmol), xantphos (18 mg, 0.03 mmol), DIEA (0.1 mL mg, 0.61 mmol), and dioxane (5 mL) were mixed uniformly and reacted under nitrogen atmosphere at 130°C in a microwave oven for 1 h. LCMS monitored the reaction completion, and the mixture was directly dried and purified by column chromatography using DCM / MeOH (10 / 1) to obtain the product, compound A07-2 (190 mg, yield: 99%). MS: 632.29 [M+H] +

[0659] Step 2: Synthesis of compound A07-3

[0660] Compound A07-2 (50 mg, 0.09 mmol) was dissolved in DCM (5 mL) and trifluoroacetic acid (2 mL) was added under ice-cooling. The mixture was allowed to react at room temperature for 1 h. LCMS monitored the reaction completion and the mixture was concentrated to afford crude compound A07-3 (90 mg), which was used directly in the next reaction. MS: 532.24 [M+H] +

[0661] Step 3: Synthesis of Compound A07

[0662] The crude compound A07-3 (90 mg) from the previous step was dissolved in DCM (5 mL). Formaldehyde (5.09 mg, 0.18 mmol) and sodium triacetoxyborohydride (36 mg, 0.18 mmol) were added sequentially and allowed to react at room temperature for 1 h. The reaction was monitored for completion by LCMS. Prep-HPLC was performed using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 mins) to obtain the product, compound A07 (87 mg, 94% yield). MS: 546.26 [M+H] +

[0663] Example 8 Synthesis of Compound A08

[0664] 1 1 , 2 6 -Dimethyl-5- 6 -((4-methylpiperazin-1-yl)amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0665] Step 1: Synthesis of Compound A08

[0666] The synthesis method of compound A08 is the same as that of compound A03-9, except that compound A03-8 is replaced by compound A08-1. MS of compound A08: 530.29 [M+H] +

[0667] Example 10 Synthesis of Compound A10

[0668] 1 1 , 2 6 -Dimethyl-5- 6 -((1'-methyl-[1,4'-dipiperidinyl]-4-yl)thio)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0669] Step 1: Synthesis of Compound A10

[0670] The synthesis method of compound A10 is the same as that of compound A07, except that formaldehyde is replaced with 1-methylpiperidin-4-one. Prep-HPLC preparation yields the product compound A10 (87 mg, yield: 94%). MS of compound A10: 629.33 [M+H] +

[0671] Example 11 Synthesis of Compound A11

[0672] (S)-2-(4-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-1-methylpiperazin-2-yl)acetonitrile

[0673] Step 1: Synthesis of compound A11-2

[0674] The synthesis method of compound A11-2 is the same as that of compound A03-9, except that compound A03-8 is replaced by compound A11-1, and compound A03-7 is replaced by compound A18-1. MS of compound A11-2: 770.41 [M+H] +

[0675] Step 2: Synthesis of compound A11-3

[0676] The synthesis method of compound A11-3 is the same as that of compound A07-3, except that compound A07-2 is replaced by compound A11-2. MS of compound A11-3: 540.28 [M+H] +

[0677] Step 3: Synthesis of Compound A11

[0678] The synthesis method of compound A11 is the same as that of compound A07, except that compound A07-3 is replaced by compound A11-3. MS of compound A11: 554.29 [M+H] +

[0679] Example 12 Synthesis of Compound A12

[0680] 1 1 , 2 6 -Dimethyl-5- 6 -((4-(1-(methylsulfonyl)azetidin-3-yl)piperazin-1-yl)methyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0681] Step 1: Synthesis of compound A12-1

[0682] Palladium acetate (0.013 g, 0.059 mmol), n-butyldi(1-adamantyl)phosphine (0.042 g, 0.118 mmol) and sodium formate (0.667 g, 9.81 mmol) were placed in a reaction flask, replaced with nitrogen three times, and a solution of A02-8 (0.500 g, 0.982 mmol) in N,N-dimethylformamide (10 mL) and a mixture of formic acid (0.148 mL) and acetic anhydride (0.371 mL) were added. The mixture was stirred at 30°C for 1 h, triethylamine (0.497 g, 4.91 mmol) was added, and stirring was continued at 110°C for 3 h. LCMS monitoring was performed. After the reaction was completed, the mixture was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (DCM / MeOH = 10 / 1) to give the product compound A12-1 (300 mg, 67%). MS:445.19[M+H] +

[0683] Step 2: Synthesis of compound A12-2

[0684] Compound A12-1 (222 mg, 0.5 mmol) was added to THF (10 mL), followed by tert-butyl 3-(piperazin-1-yl)azetidine-1-carboxylate (241 mg, 1 mmol) and 2-3 drops of acetic acid. The mixture was mixed evenly, cooled to 0°C, and sodium triacetoxyborohydride (212 mg, 1 mmol) was slowly added. After the addition was complete, the mixture was allowed to warm to room temperature and reacted for 2 h. LCMS monitored the reaction completion. 20 mL of water was added to quench the reaction, followed by extraction with DCM (10 mL*3). The organic phases were combined and washed with saturated brine. Purification by column chromatography (DCM / MeOH = 10 / 1) gave product A12-2 (117 mg, yield: 35%), MS: 670.38 [M+H] +

[0685] Step 3: Synthesis of compound A12-3

[0686] Compound A12-2 (100 mg, 0.15 mmol) was added to DCM (5 mL) and stirred to dissolve. 4N hydrochloric acid in dioxane (1 mL) was added dropwise. After addition, the mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion. The crude product A12-3 was concentrated and used directly in the next step. MS: 570.33 [M+H] +

[0687] Step 4: Synthesis of Compound A12

[0688] Crude compound A12-3 (20 mg, 0.04 mmol) was added to DCM (5 mL), followed by DIEA (0.02 mL, 0.12 mmol). The temperature was lowered to 0°C, and methylsulfonyl chloride (6.04 mg, 0.05 mmol) was added dropwise. After the addition was complete, the reaction was stirred at room temperature for 1 hour. LCMS was used to monitor the reaction until completion. The organic phase was washed with 5 mL of water, dried, concentrated, and purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 min) to afford product A12 (4.3 mg, 19% yield). MS: 648.30 [M+H] +

[0689] Example 13 Synthesis of Compound A13

[0690] 1 1 , 2 6 -Dimethyl-5- 6 -(3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0691] Step 1: Synthesis of compound A13-1

[0692] Compound A18-1 (100 mg, 0.16 mmol) was added to dioxane (5 mL), followed by tert-butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (81.28 mg, 0.32 mmol), Pd2(dba)3 (29.3 mg, 0.03 mmol), Xantphos (27.72 mg, 0.05 mmol), and sodium tert-butoxide (46.07 mg, 0.48 mmol). After the addition was complete, the atmosphere was purged with nitrogen three times. The temperature was raised to 100°C and the reaction was allowed to proceed for 2 h. LCMS was used to monitor the reaction until completion. 20 mL of DCM was added to dilute the mixture, followed by washing with water and saturated brine. The organic phase was concentrated. The crude product A13-1 was obtained and used directly in the next step. MS: 799.46 [M+H]. +

[0693] Step 2: Synthesis of Compound A13

[0694] The crude product of compound A13-1 was added to DCM (5 mL) and stirred to dissolve. A 4M hydrochloric acid solution in dioxane (1 mL) was added dropwise and stirred for 30 minutes. A solid precipitated and was filtered. The filter cake was rinsed with DCM. The filter cake was added to DCM (5 mL) and trifluoroacetic acid (2 mL) was added dropwise. After the addition was complete, the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until complete. The product was concentrated and purified by Prep-HPLC using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to obtain product A13. MS: 569.33 [M+H] +

[0695] Example 14 Synthesis of Compound A14

[0696] 1 1 , 2 6 -Dimethyl-5- 6 -(thiomorpholinomethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0697] Step 1: Synthesis of compound A14

[0698] Compound A02-8 (99 mg, 0.2 mmol) and potassium trifluoro(thiomorpholinomethyl)borate (66.9 mg, 0.3 mmol) were added to a reaction flask, followed by dioxane (1.2 mL) and water (0.3 mL), potassium carbonate (82.8 mg, 0.6 mmol) and Pd(dppf)Cl2 (15 mg, 0.02 mmol), and the atmosphere was replaced with nitrogen. The reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. After the disappearance of the starting material, heating was stopped and the sample was mixed with silica gel and passed through the column. The eluent was changed from pure PE to pure EA, and the crude product was concentrated. Prep-HPLC was performed on a Luna C18 column, 30 x 250 mm, and the mobile phase was (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 30 min). The preparative solution was rotary evaporated to remove the organic solvent and lyophilized to obtain 9 mg of the product (95% purity, 8% yield). MS: 532.24 [M+H] +

[0699] Example 16 Synthesis of Compound A16

[0700] (S)-N-(2-(4-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-1-methylpiperazin-2-yl)ethyl)acrylamide

[0701] Step 1: Synthesis of compound A16-1

[0702] Compound A11 (60 mg, 0.11 mmol), Raney nickel (46 mg, 0.54 mmol), and MeOH (NH3, 4 M, 5 mL) were mixed uniformly, the hydrogen atmosphere was replaced, and the mixture was allowed to react at room temperature for 3 h. LCMS monitoring indicated 50% product formation. The mixture was filtered, dried, and then preparatively filtered through a reverse phase chromatography system (mobile phase A: 0.05% FA in water; mobile phase B: ACN) with a gradient of 0-75% B over 20 min to afford compound A16-1 (15 mg, 25% yield). MS: 558.32 [M+H] +

[0703] Step 2: Synthesis of compound A16

[0704] The synthesis method of compound A16 is the same as that of compound A03, except that compound A03-10 is replaced by A16-1. MS of compound A16: 612.33 [M+H] +

[0705] Example 18 Synthesis of Compound A18

[0706] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0707] Step 1: Synthesis of compound A18-1

[0708] A02-8 (0.500 g, 0.982 mmol) was added to N,N-dimethylformamide (10 mL), followed by DIEA (0.388 g, 3 mmol) and SEMCl (333 mg, 2 mmol) dropwise. After the addition was complete, the mixture was heated to 60°C and reacted for 2 hours. After completion of the reaction, the temperature was lowered and the reaction mixture was poured into 50 mL of water with stirring. The precipitated solid was filtered, the filter cake was rinsed with water, and dried to obtain the product, compound A18-1 (510 mg, yield: 86%). MS: 625.19, 627.19 [M+H] + .

[0709] Step 2: Synthesis of compound A18-2

[0710] Compound A18-1 (100 mg, 0.16 mmol) was added to dioxane (5 mL), followed by 3-methyl-3,9-diazaspiro[5,5]undecane (53.78 mg, 0.32 mmol), Pd2(dba)3 (29.3 mg, 0.03 mmol), Xantphos (27.72 mg, 0.05 mmol), and sodium tert-butoxide (46.07 mg, 0.48 mmol). After the addition was complete, the atmosphere was purged with nitrogen three times. The temperature was raised to 100°C and the reaction was allowed to proceed for 2 h. LCMS was used to monitor the reaction until completion. The mixture was diluted with 20 mL of DCM, washed with water, and then washed with saturated brine. The organic phase was concentrated. The crude product A18-2 was obtained and used directly in the next step. MS: 713.42 [M+H]. +

[0711] Step 3: Synthesis of compound A18

[0712] The crude product of compound A18-2 was added to DCM (5 mL) and stirred to dissolve. Trifluoroacetic acid (TFA) (2 mL) was added dropwise. After addition, the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion. The product was concentrated and the residue was purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to obtain product A18 (27 mg). MS: 583.34 [M+H] +

[0713] Example 20 Synthesis of Compound A20

[0714] N-(2-((1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)(4-methylpiperazin-1-ylamino)ethyl)acrylamide

[0715] Step 1: Synthesis of compound A20-1

[0716] The synthesis method of compound A20-1 is the same as that of compound A18-2, except that the compound 3-methyl-3,9-diazaspiro[5,5]undecane is replaced by 1-amino-4-methylpiperazine. MS of compound A20-1: 660.37 [M+H] +

[0717] Step 2: Synthesis of compound A20-3

[0718] Compound A20-1 (60 mg, 0.09 mmol) was added to ACN (4 mL), followed by A20-2 (40.74 mg, 0.18 mmol), potassium carbonate (37.69 mg, 0.27 mmol), and potassium iodide (15.09 mg, 0.09 mmol). After the addition was complete, the atmosphere was purged with nitrogen three times and the temperature was raised to 80°C for overnight reaction. The mixture was filtered, dried, and preparatively purified by reverse phase chromatography (mobile phase A: 0.05% water; mobile phase B: ACN; gradient 0-75% B over 20 min) to afford compound A20-3 (16 mg, yield: 22%), MS: 803.47 [M+H] + .

[0719] Step 3: Synthesis of compound A20-4

[0720] The synthesis method of compound A20-4 is the same as that of compound A18, except that compound A18-2 is replaced by A20-3. MS of compound A20-4: 573.33 [M+H] +

[0721] Step 4: Synthesis of Compound A20

[0722] The synthesis method of compound A20 is the same as that of compound A03, except that compound A03-10 is replaced by A20-4. MS of compound A20: 627.34 [M+H] +

[0723] Example 21 Synthesis of Compound A21

[0724] 5 6 -((2-methoxy-4-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)phenyl)amino)-1- ... 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0725] Step 1: Synthesis of compound A21-3

[0726] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by dioxane (3.5 mL), sodium tert-butoxide (145 mg, 1.5 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and compound A21-2 (289 mg, 1 mmol). The atmosphere was then purged with nitrogen and allowed to react at 90°C for 3 hours. The reaction was monitored by LCMS. Upon completion, the sample was added with silica gel and passed through a column, with the eluents switching from pure PE to pure EA. The product was concentrated to give 196 mg (yield: 46%). MS: 834.48 [M+H] +

[0727] Step 2: Synthesis of compound A21

[0728] Compound A21-3 (196 mg, 0.23 mmol) was added to a reaction flask, followed by methanol (2 mL) as solvent and trifluoroacetic acid (1 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. The reaction was stopped and the solvent removed by rotary evaporation. The crude product was then subjected to Prep-HPLC on a Luna C18 column, 30 x 250 mm, using a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). The preparative solution was lyophilized to yield 30 mg of the product (yield: 19%). MS: 704.40 [M+H] +

[0729] Example 23 Synthesis of Compound A23

[0730] Diethyl (E)-(1 1 , 2 6 -Dimethyl-3-oxo-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)phosphonate

[0731] Step 1: Synthesis of compound A23-1

[0732] Compound A18-1 (100 mg, 0.16 mmol) was added to tetrahydrofuran (5 mL), followed by diethyl phosphite (66.24 mg, 0.48 mmol), Pd(PPh3)4 (29.3 mg, 0.03 mmol), and cesium carbonate (156.39 mg, 0.48 mmol). After the addition was complete, the atmosphere was purged with nitrogen three times. Microwave reaction was performed at 120°C for 90 min. LCMS monitoring was performed until the reaction was complete. The mixture was diluted with 20 mL of DCM, washed with water, and then washed with saturated brine. The organic phase was concentrated. The crude product A23-1 was obtained and used directly in the next step. MS: 683.31 [M+H]. +

[0733] Step 2: Synthesis of compound A23

[0734] The crude product of compound A23-1 was added to DCM (5 mL) and stirred to dissolve. Trifluoroacetic acid (TFA) (2 mL) was added dropwise. After addition, the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion. The product was concentrated and the residue was purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to obtain product A23 (9 mg). MS: 553.23 [M+H] +

[0735] Example 24 Synthesis of Compound A24

[0736] 1 1 -methyl-5 6 -(1-methyl-1,9-diazaspiro[5.5]undec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0737] Step 1: Synthesis of compound A24-2

[0738] Compound A24-1 (255 mg, 1 mmol) was added to a reaction flask, tetrahydrofuran (3 mL) was added as solvent, and formaldehyde (2 mL, 1 M) solution was added. The mixture was stirred for 1 hour, and sodium cyanoborohydride (125 mg, 2 mmol) was added and stirred for another 1 hour. The reaction was monitored by LCMS. The reaction was stopped and quenched by adding water (5 mL). Ethyl acetate (25 mL) was added for extraction. The liquids were separated, and the organic phase was removed by rotary evaporation. Silica gel was added and the sample was passed through a column. The eluent was changed from pure PE to pure PE:EA = 1:1. The product was concentrated to obtain 206 mg (yield: 77%). MS: 269.22 [M+H] +

[0739] Step 2: Synthesis of compound A24-3

[0740] Compound A24-2 (206 mg, 0.77 mmol) was added to a reaction flask, followed by methanol (1.5 mL) and dioxane hydrochloride (1 mL, 4 M). The mixture was stirred at room temperature for 1 hour. LCMS was used to monitor the reaction. The solvent was removed by rotary evaporation. Toluene (25 mL) was added and the solvent was removed by rotary evaporation to obtain 90 mg of the crude product (yield: 70%). MS: 169.16 [M+H] +

[0741] Step 3: Synthesis of compound A24-4

[0742] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by dioxane (3.5 mL), sodium tert-butoxide (145 mg, 1.5 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and A24-3 (90 mg, 0.53 mmol). The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added with silica gel and passed through a column. The eluent was then rinsed with pure PE and then pure EA. The crude product (190 mg, 53% yield) was obtained by concentration. MS: 699.41 [M+H] +

[0743] Step 4: Synthesis of Compound A24

[0744] Compound A24-4 ​​(190 mg, 0.27 mmol) was added to a reaction flask, followed by methanol (2.0 mL) and trifluoroacetic acid (0.5 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the solvent was removed by rotary evaporation. The crude product was then sent to Prep-HPLC for preparation using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile varied from 15% to 40% over 20 min). The organic phase was removed by rotary evaporation and lyophilized to yield 80 mg of the product (yield: 52%). MS: 569.33 [M+H] +

[0745] Example 25 Synthesis of Compound A25

[0746] (E)-5 6 -(2-Acryloyl-2,9-diazaspiro[5.5]undec-9-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0747] Step 1: Synthesis of compound A25-2

[0748] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by dioxane (3.5 mL) as solvent. Sodium tert-butoxide (145 mg, 1.5 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and A25-1 (190 mg, 0.75 mmol) were then added. The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added with silica gel and passed through a column. The eluent was then changed from pure PE to pure EA. Concentration afforded 230 mg of the crude product (yield: 58%). MS: 799.46 [M+H] +

[0749] Step 2: Synthesis of compound A25-3

[0750] Compound A25-2 (230 mg, 0.29 mmol) was added to a reaction flask, followed by dichloromethane (3 mL) and then dioxane hydrochloride (1 mL, 4 M). The mixture was stirred at room temperature for 2 hours. The reaction was monitored by LCMS. The reaction was stopped and the solvent was removed by rotary evaporation to obtain 130 mg of the crude product (yield: 65%). MS: 699.41 [M+H] +

[0751] Step 3: Synthesis of compound A25-4

[0752] Compound A25-3 (130 mg, 0.19 mmol) was added to a reaction flask, followed by dichloromethane (2 mL) and triethylamine (61 mg, 0.6 mmol). Acryloyl chloride (27 mg, 0.3 mmol) was added dropwise at 0°C and stirred at 0°C for 1 hour. The reaction was monitored by LCMS. Upon completion, pure water (3 mL) was added dropwise to quench the reaction. Dichloromethane (15 mL) was added for extraction and the organic phase was removed by rotary evaporation to obtain 80 mg of the crude product (yield: 56%). MS: 753.42 [M+H] +

[0753] Step 4: Synthesis of Compound A25

[0754] Compound A25-4 (80 mg, 0.11 mmol) was added to a reaction flask, followed by methanol (1.0 mL) and trifluoroacetic acid (0.3 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the solvent was removed by rotary evaporation. The crude product was then sent to Prep-HPLC for preparation using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). The organic phase was removed by rotary evaporation and lyophilized to yield 30 mg of the product (yield: 46%). MS: 623.34 [M+H] +

[0755] Example 26 Synthesis of Compound A26

[0756] (E)-1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,9-diazaspiro[5.5]undec-9-yl)-5 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0757] Step 1: Synthesis of compound A26-2

[0758] Compound A26-1 (253 mg, 1 mmol) was added to a reaction flask, followed by tetrahydrofuran (3 mL) solvent. LiAlH4 (1.5 mL, 1 M) was added dropwise at 0°C, and the temperature was raised to 70°C for 2 hours. The reaction was monitored by LCMS. Upon completion, heating was discontinued, and water (1 mL) was added to the reaction solution at 0°C, followed by sodium hydroxide (1 mL, 1 M) solution, followed by water (3 mL) and tetrahydrofuran (10 mL). The mixture was stirred for 10 minutes, filtered, and the filtrate was evaporated to remove the solvent to obtain 123 mg of crude product (yield: 73%). MS: 169.16 [M+H] +

[0759] Step 2: Synthesis of compound A26-3

[0760] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by dioxane (3.5 mL) as solvent. Sodium tert-butoxide (145 mg, 1.5 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and A26-2 (123 mg, 0.73 mmol) were then added. The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added with silica gel and passed through a column. The eluent was then changed from pure PE to pure EA, and the crude product (230 mg, 65% yield) was obtained by concentration. MS: 713.42 [M+H] +

[0761] Step 3: Synthesis of compound A26

[0762] Compound A26-3 (230 mg, 0.32 mmol) was added to a reaction flask, followed by methanol (2.0 mL) and trifluoroacetic acid (0.5 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the solvent was removed by rotary evaporation. The crude product was then sent for Prep-HPLC preparation using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile varied from 15% to 40% over 20 min). The organic phase was removed by rotary evaporation and lyophilized to yield 130 mg of the product (yield: 70%). MS: 583.34 [M+H] +

[0763] Example 27 Synthesis of Compound A27

[0764] 5 6 -(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinane-2-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-3-one

[0765] Step 1: Synthesis of compound A27-2

[0766] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by tetrahydrofuran (3.5 mL), cesium carbonate (487 mg, 1.5 mmol), A27-1 (150 mg, 1.0 mmol), and Pd(dppf)Cl2 (37 mg, 0.05 mmol). The atmosphere was purged with nitrogen and the reaction was carried out in a microwave reactor at 120°C for 1 hour. LCMS was used to monitor the reaction. Heating was stopped, and the sample was added to a silica gel column. The eluent was then rinsed from pure PE to pure EA, and the crude product (190 mg, 55% yield) was obtained by concentration. MS: 695.31 [M+H] +

[0767] Step 2: Synthesis of compound A27

[0768] Compound A27-2 (180 mg, 0.27 mmol) was added to a reaction flask, followed by methanol (2.0 mL) and trifluoroacetic acid (0.5 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the solvent was removed by rotary evaporation. The crude product was then sent to Prep-HPLC for preparation using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 15% to 50% over 20 min). The organic phase was removed by rotary evaporation and lyophilized to obtain 90 mg of the product (yield: 59%). MS: 565.23 [M+H] +

[0769] Example 28 Synthesis of Compound A28

[0770] 5 6 -(1-acryloyl-1,9-diazaspiro[5.5]undec-9-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0771] Step 1: Synthesis of compound A28-2

[0772] Compound A28-1 (253 mg, 1 mmol) was added to a reaction flask, and methanol (2.0 mL) was added as solvent. Dioxane hydrochloride (1 mL, 1 M) was added dropwise, and the mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the solvent was removed by rotary evaporation to obtain 130 mg of the product (yield: 85%). MS: 155.15 [M+H] +

[0773] Step 2: Synthesis of compound A28-3

[0774] Compound A18-1 (312 mg, 0.5 mmol) was added to a reaction flask, followed by dioxane (3.5 mL) as solvent. Sodium tert-butoxide (145 mg, 1.5 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and compound A28-2 (130 mg, 0.85 mmol) were then added. The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added with silica gel and passed through a column. The eluent was then changed from pure PE to pure EA. Concentration afforded 210 mg of the product (yield: 60%). MS: 699.41 [M+H]. +

[0775] Step 3: Synthesis of compound A28-4

[0776] Compound A28-3 (210 mg, 0.3 mmol) was added to a reaction flask, followed by dichloromethane (2 mL) and triethylamine (101 mg, 1.0 mmol). Acryloyl chloride (27 mg, 0.3 mmol) was added dropwise at 0°C and stirred at 0°C for 1 hour. The reaction was monitored by LCMS. Upon completion, pure water (3 mL) was added dropwise to quench the reaction. Dichloromethane (15 mL) was added for extraction and the organic phase was removed by rotary evaporation to obtain 110 mg of the product (49% yield). MS: 753.42 [M+H] +

[0777] Step 4: Synthesis of Compound A28

[0778] Compound A28-4 (110 mg, 0.15 mmol) was added to a reaction flask, followed by methanol (1.0 mL) and trifluoroacetic acid (0.5 mL) dropwise. The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the solvent was removed by rotary evaporation. The crude product was then sent for Prep-HPLC preparation using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 15% to 50% over 20 min). The organic phase was removed by rotary evaporation and lyophilized to yield 80 mg of the product (yield: 86%). MS: 623.34 [M+H] +

[0779] Example 29 Synthesis of Compound A29

[0780] 1 1 , 2 6 -Dimethyl-5-6 -(9-(2,2,2-trifluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0781] Step 1: Synthesis of compound A29

[0782] The crude product of compound A13 (91 mg, 0.16 mmol) was added to ACN (5 mL), followed by the addition of K2CO3 (66.34 mg, 0.48 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (74.24 mg, 0.32 mmol). After the addition was complete, the mixture was heated to 60°C and reacted for 2 hours. The reaction was monitored by LCMS until completion, after which the mixture was concentrated and the residue was purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to afford product A29 (15 mg, 14% yield). MS: 651.33 [M+H] +

[0783] Example 30 Synthesis of Compound A30

[0784] 2-(9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)acetonitrile

[0785] Step 1: Synthesis of compound A30

[0786] Compound A13 (30 mg, 0.05 mmol) was added to DCM (5 mL), followed by Et3N (15.23 mg, 0.15 mmol) and bromoacetonitrile (8.4 mg, 0.07 mmol). After addition, the mixture was stirred at room temperature overnight. The reaction was monitored by LCMS until complete, washed with water, and the organic phase was concentrated. The residue was then purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to afford product A29 (2.1 mg, 7% yield). MS: 608.34 [M+H] +

[0787] Example 47 Synthesis of Compound A47

[0788] 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[5.5]undec-8-en-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0789] Step 1: Synthesis of compound A47-2

[0790] In a 500 mL three-necked flask, compound A47-1 (5 g, 27.58 mmol) was dissolved in tetrahydrofuran (100 mL). Under nitrogen, NaHMDS (41.37 mL, 41.37 mmol) was added dropwise at -78°C. After the addition was complete, the mixture was stirred at -78°C for 0.5 h. N-phenylbis(trifluoromethanesulfonyl)imide (19.7 g, 55.16 mmol) was dissolved in tetrahydrofuran (100 mL) and added dropwise to the above solution at -78°C. After the addition was complete, the mixture was stirred at -78°C for 1 h. TLC confirmed the complete reaction of the starting material. 500 mL of water was added, and the aqueous phase was extracted with ethyl acetate (3 x 500 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1). Compound A47-2 (6.50 g, 20.74 mmol, yield: 75.21%) was obtained as a yellow oil.

[0791] Step 2: Synthesis of compound A47-3

[0792] In a 500 mL single-necked flask, compound A47-2 (6.50 g, 20.74 mmol), NaOAc (2.55 g, 31.11 mmol), Pd(dppf)Cl2 (3 g, 4.14 mmol), and B2pin2 (10.5 g, 41.4 mmol) were added to 1,4-dioxane (200 mL). The mixture was heated to 100°C and stirred overnight under nitrogen. TLC monitored the reaction completion. After adding 500 mL of water, the aqueous phase was extracted with ethyl acetate (3 x 500 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1). Compound A47-3 (4.50 g, 15.45 mmol, 74.50% yield) was obtained as a yellow oil.

[0793] Step 3: Synthesis of compound A47

[0794] In a 100 mL single-necked vial, compound A47-3 (100 mg, 0.34 mmol), A02-8 (170 mg, 0.34 mmol), Pd(dppf)Cl2 (50 mg, 0.07 mmol), and Na2CO3 (72 mg, 0.68 mmol) were added to a mixture of 1,4-dioxane (40 mL) and H2O (10 mL). The mixture was heated to 100°C under nitrogen and stirred for 12 h. The reaction was monitored for completion by LCMS and cooled to room temperature. 200 mL of water was added, and the aqueous phase was extracted with ethyl acetate (3 x 200 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (petroleum ether:ethyl acetate = 1:1). Compound A47 (50 mg, 16.36 mmol, yield: 25.35%) was obtained as a white solid. MS: 580.34 [M+H] +

[0795] Using intermediate A02-8 as raw material, the following final product was prepared according to a similar method to the above-mentioned final product:

[0796] Example 50 Synthesis of Compound A50

[0797] (S)-1 1 , 2 6 , 5 3 -Trimethyl-5 1 , 5 2 , 5 3 , 5 4 , 54a , 5 5 -Hexahydro-1 1 H, 5 10 H-11-oxa-4-aza-5(9,10)-imidazo[4′,5′:4,5]benzo[1,2-b]pyrazino[1,2-d][1,4]oxazine-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecyl-3-one

[0798] Step 1: Synthesis of compound A50-3

[0799] Compound A50-2 (10.2 g, 50 mmol) was added to a reaction flask, followed by DMF (100 mL) and DIPEA (16.8 g, 150 mmol). Finally, A50-1 (10.8 g, 50 mmol) was added and stirred at room temperature for 3 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was poured into water (350 mL) and stirred for 10 minutes. The mixture was extracted with ethyl acetate (1000 mL), dried, and the solvent removed by rotary evaporation to obtain 18.5 g of the crude product (yield: 92.5%). MS: 401.14 [M+H] +

[0800] Step 2: Synthesis of compound A50-4

[0801] Compound A50-3 (18.5 g, 46.3 mmol) was added to a reaction flask, followed by DMF (185 mL) and NaH (2.23 g, 93 mmol) at 0°C. The mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was poured into water (350 mL) and stirred for 10 minutes. Ethyl acetate (1000 mL) was added for extraction, dried, and filtered through a column with silica gel. The eluent was changed from pure PE to PE:EA = 1:1. Concentration afforded 16 g of the product (yield: 91%). MS: 381.13 [M+H] +

[0802] Step 3: Synthesis of compound A50-5

[0803] Compound A50-4 (16 g, 42.1 mmol) was added to a reaction flask, followed by methanol (160 mL). Dioxane hydrochloride (36 mL, 4 M) was added dropwise at 0°C and stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the solvent was removed by rotary evaporation to obtain 10 g of the crude product (yield: 85%). MS: 281.08 [M+H] +

[0804] Step 4: Synthesis of compound A50-6

[0805] Compound A50-5 (10 g, 35.7 mmol) was added to a reaction flask, followed by tetrahydrofuran (100 mL) and formaldehyde solution. The mixture was stirred at room temperature for 1 hour. Sodium cyanoborohydride (3.15 g, 50 mmol) was added and stirring continued for 1 hour. LCMS was used to monitor the reaction. Upon completion, water (300 mL) and ethyl acetate (1000 mL) were added to the reaction system, and the mixture was separated by extraction. The organic phase was removed by rotary evaporation to obtain 9 g of the crude product (yield: 86%). MS: 295.10 [M+H] +

[0806] Step 5: Synthesis of compound A50-7

[0807] Compound A50-7 (9 g, 30.6 mmol) was added to a reaction flask, followed by methanol (90 mL) and palladium on carbon (900 mg). The mixture was replaced with hydrogen and stirred at room temperature for 3 hours. LCMS was used to monitor the reaction, indicating completion. The filtrate was filtered and the solvent was removed by rotary evaporation to obtain 6.3 g of the crude product (yield: 88%). MS: 235.15 [M+H] +

[0808] Step 6: Synthesis of Compound A50-8

[0809] Compound A50-7 (6.3 g, 26.9 mmol) was added to a reaction flask, followed by DMF (63 mL), followed by compound A50-16 (5.81 g, 35 mmol) and potassium carbonate (11.05 g, 80 mmol). The mixture was stirred at room temperature for 3 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was poured into water (150 mL), stirred for 10 minutes, and extracted with ethyl acetate (500 mL). The mixture was separated and the solvent removed by rotary evaporation. Silica gel was added to the sample and passed through a column. The eluent was then rinsed with pure PE and then pure EA. The product was concentrated to give 6.5 g (yield: 76%). MS: 321.22 [M+H] +

[0810] Step 7: Synthesis of Compound A50-9

[0811] Compound A50-8 (6.5 g, 20.3 mmol) was added to a reaction flask, followed by methanol (50 mL) and water (15 mL). Cyanogen bromide (3.18 g, 30 mmol) was then added and allowed to react at 60°C for 2 hours. LCMS was used to monitor the reaction. Upon completion, the sample was added to a silica gel column and flushed with eluents ranging from pure PE to pure EA. The product was concentrated to yield 6 g (yield: 86%). MS: 346.22 [M+H] +

[0812] Step 8: Synthesis of Compound A50-10

[0813] Compound A50-9 (6 g, 17.3 mmol) was added to a reaction flask, followed by dichloromethane (60 mL) and Boc2O (6.36 g, 30 mmol). The mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, water (150 mL) was added to quench the reaction, and the mixture was extracted with dichloromethane (500 mL). The mixture was dried and the solvent removed by rotary evaporation to obtain 6.5 g of the product (yield: 84%). MS: 446.27 [M+H] +

[0814] Step 9: Synthesis of Compound A50-11

[0815] Compound A50-10 (6.5 g, 14.6 mmol) was added to a reaction flask, followed by dichloromethane (65 mL) and triethylamine (4.55 g, 45 mmol). MsCl (1.72 g, 15 mmol) was added dropwise at 0°C and stirred at room temperature for 1 hour. The reaction was monitored by LCMS. Upon completion, the mixture was quenched with water (150 mL) and extracted with dichloromethane (500 mL). The mixture was separated and the solvent was removed by rotary evaporation to obtain 6.5 g of the crude product (yield: 85%). MS: 524.25 [M+H] +

[0816] Step 10: Synthesis of Compound A50-13

[0817] Compound A50-11 (6.5 g, 12.4 mmol) was added to a reaction flask, followed by DMF (65 mL), compound A50-12 (3.71 g, 15 mmol) and potassium carbonate (5.25 g, 38 mmol), and the mixture was stirred at room temperature for 3 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was added to water (150 mL) and stirred for 10 minutes. Ethyl acetate (500 mL) was added for extraction. The mixture was separated, and the sample was mixed with silica gel and passed through a column. The eluent was changed from pure PE to pure EA, and the mixture was concentrated to obtain 6.5 g of the product (yield: 78%). MS: 675.35 [M+H] +

[0818] Step 11: Synthesis of Compound A50-14

[0819] Compound A50-13 (6.5 g, 9.6 mmol) was added to a reaction flask, followed by methanol (65 mL). Dioxane hydrochloride (9.6 mL, 4 M) was added dropwise at 0°C and stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the solvent was removed by rotary evaporation to obtain 5 g of the product (yield: 91%). MS: 575.30 [M+H] +

[0820] Step 12: Synthesis of Compound A50-15

[0821] Compound A50-14 (5 g, 8.7 mmol) was added to a reaction flask, and methanol (50 mL) and water (10 mL) were added. Lithium hydroxide (480 mg, 20 mmol) was then added and stirred at room temperature for 3 hours. LCMS was used to monitor the reaction. Upon completion, the organic solvent was removed by rotary evaporation, water (35 mL) was added, and 2N hydrochloric acid was added dropwise to adjust the pH to 3. A solid precipitated. The mixture was stirred for 10 minutes, filtered, and the filter cake was dried to obtain 3.9 g of the product (yield: 80%). MS: 561.29 [M+H] +

[0822] Step 13: Synthesis of Compound A50

[0823] Compound A50-15 (560 mg, 1 mmol) was added to a reaction flask, followed by DMF (6 mL) solvent, condensing agent HATU (456 mg, 1.2 mmol) and DIPEA (387 mg, 3 mmol), and the mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was added to water (15 mL) and stirred for 10 minutes. The mixture was extracted with ethyl acetate (50 mL), dried, and the solvent removed by rotary evaporation. The crude product was then subjected to Prep-HPLC on a Luna C18 column, 30 x 250 mm, using a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile was varied from 20% to 50% over 20 minutes). The preparative solution was lyophilized to yield 190 mg of the product (yield: 35%). MS: 543.28 [M+H] +

[0824] The following final product was prepared in a similar manner to Example 50

[0825] Example 40 Synthesis of Compound A40

[0826] 26 -Chloro-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0827] Step 1: Synthesis of compound A40-1

[0828] In a 500 mL single-necked flask, bis(pinacol)diboronate (27.33 g, 107.62 mmol) was suspended in MTBE (250 mL). The temperature was raised to 70°C, approximately one-third of the solvent was evaporated, and the mixture was cooled to room temperature. Methoxy(cyclooctadiene)iridium dimer (0.89 g, 1.34 mmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (0.72 g, 2.68 mmol) were added and stirred at room temperature for 10 min. The reaction mixture was then added to a solution of methyl 2-chloroisonicotinate (15.05 g, 87.71 mol) in MTBE (20 mL) and stirred at room temperature for 90 h. The mixture was concentrated under reduced pressure, and the residue was added to n-hexane (120 mL). The mixture was stirred at room temperature overnight, filtered, and the filter cake was rinsed with n-hexane to obtain product A40-1 (16.92 g, 56.86 mmol, yield: 64.8%). MS:298.10[M+H] +

[0829] Step 2: Synthesis of compound A40-2

[0830] In a reaction flask, 5-hydroxy-1-methylpyrazole (2.50 g, 25.48 mmol) and potassium carbonate (7.55 g, 54.63 mol) were suspended in acetonitrile (150 mL). The mixture was cooled to 0°C in an ice-water bath. A solution of SEM-Cl (7.58 g, 45.47 mmol) in acetonitrile (10 mL) was added dropwise. After the addition was complete, the mixture was warmed to room temperature and reacted for 1.5 hours. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was separated by column chromatography (DCM:MeOH:NH3 = 94.5:5:0.5) to obtain product A40-2 (4.83 g, 21.15 mmol, 83.0% yield). MS: 229.13 [M+H] +

[0831] Step 3: Synthesis of compound A40-3

[0832] A40-2 (3.80 g, 16.64 mmol) and acetonitrile (100 mL) were added to a reaction flask. The temperature was lowered to 0-5°C, and N-iodosuccinimide (3.71 g, 16.5 mmol) was slowly added. After the addition was complete, the reaction was maintained at 0-5°C for 2 hours. N-iodosuccinimide (0.32 g, 1.42 mmol) was added and the reaction was continued at 0-5°C for 30 minutes. The mixture was allowed to warm to room temperature, and 200 mL of water was added. DCM extraction was performed (100 mL x 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography (PE:EA = 10:1-2:1) to obtain product A40-3 (4.12 g, 11.63 mmol, yield: 69.8%). MS: 355.03 [M+H] +

[0833] Step 4: Synthesis of compound A40-4

[0834] Compound A40-1 (4.20 g, 14.11 mmol) was added to toluene (70 mL), followed by A40-3 (4.00 g, 11.29 mmol), tris(dibenzylideneacetone)dipalladium (268.8 mg, 0.29 mmol), n-butyldi(1-adamantyl)phosphine (290.5 mg, 0.81 mmol), cesium carbonate (11.21 g, 34.41 mmol), and water (15 mL). The atmosphere in the reaction system was replaced with nitrogen three times. Under a nitrogen balloon, the reaction was incubated at 65°C for 5 hours. The reaction was monitored for completion by LCMS. The product was cooled to room temperature, and 100 mL of water was added. The product was extracted with ethyl acetate (100 mL x 2), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography (EA:PE = 1:3) to afford compound A40-4 (2.31 g, 5.80 mmol, 51.4% yield). MS:398.12[M+H] +

[0835] Step 5: Synthesis of compound A40-5

[0836] Compound A40-4 (1.25 g, 3.14 mmol) was added to 1,4-dioxane (8 mL), followed by a solution of hydrogen chloride in 1,4-dioxane (8 mL, 4.0 M). The mixture was allowed to react at room temperature overnight. The mixture was filtered, and the filter cake was washed with 1,4-dioxane (10 mL). The filter cake was then added with water (20 mL), DCM (30 mL), and saturated aqueous potassium carbonate (20 mL). The mixture was shaken and separated. The aqueous phase was extracted with DCM (30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to yield product A40-5 (0.62 g, 2.32 mmol, yield: 73.9%). MS: 268.04 [M+H] +

[0837] Step 6: Synthesis of Compound A40-6

[0838] In a 100 mL single-necked bottle, compound A02-3 (0.76 g, 2.00 mmol), A40-5 (0.53 g, 1.98 mmol), potassium carbonate (0.56 g, 4.05 mmol), and DMF (10 mL) were mixed and reacted at 60°C for 5 h. The reaction was monitored by LCMS until complete. 30 mL of ethyl acetate was added, and the mixture was washed with 3 x 20 mL of saturated brine. The organic phase was dried and purified by column chromatography using DCM / EA = 4 / 1 to give compound A40-6 (0.96 g, 1.74 mmol, yield: 87%). MS: 552.10, 554.10 [M+H] +

[0839] Step 7: Synthesis of Compound A40-7

[0840] A40-6 (0.95 g, 1.72 mmol), iron powder (0.55 g, 9.82 mmol), ammonium chloride (0.51 g, 9.53 mmol), ethanol (6 mL), and H2O (3 mL) were mixed and reacted at 60°C for 1 h. The reaction was complete after LCMS monitoring. The mixture was filtered, cooled, and dried by spin chromatography. Compound A40-7 (0.70 g, 1.34 mmol, yield: 77.9%) was obtained by column chromatography using DCM / MeOH = 10 / 1. MS: 522.20, 524.06 [M+H] +

[0841] Step 8: Synthesis of Compound A40-8

[0842] Compound A40-7 (0.70 g, 1.34 mmol), cyanogen bromide (156.8 mg, 1.48 mmol), methanol (5 mL), and water (1 mL) were mixed uniformly and reacted at 70°C for 1 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 8-9, and the mixture was extracted with 3 x 20 mL of DCM. The mixture was concentrated under reduced pressure to obtain compound A40-8 (0.66 g, 1.20 mmol, yield: 89.5%). MS: 547.10, 549.10 [M+H] +

[0843] Step 9: Synthesis of Compound A40-9

[0844] Compound A40-8 (0.65 g, 1.19 mmol), NaOH (0.25 g, 6.25 mmol), methanol (2 mL), and water (2 mL) were mixed and reacted at room temperature for 1 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 6-7, and the mixture was extracted with 3 x 30 mL of DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the product compound A40-9 (0.58 g, yield: 91.6%). MS: 533.06, 535.06 [M+H] +

[0845] Step 10: Synthesis of Compound A40-10

[0846] Compound A40-9 (0.58 g, 1.09 mmol), DIEA (285.7 mg, 2.21 mmol), and DCM (15 mL) were mixed uniformly. HATU (0.84 g, 2.21 mmol) was added under ice-cooling. The mixture was allowed to react at 10-15°C for 30 min. The reaction was monitored by LCMS. 30 mL of water was added to quench the reaction. The mixture was then extracted with 20 mL of DCM three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and dried by spin chromatography. The mixture was purified by column chromatography using a 20 / 1 ratio of DCM to MeOH to afford A40-10 (369.4 mg, 65.7% yield). MS: 515.05, 517.05 [M+H] +

[0847] Step 11: Synthesis of Compound A40

[0848] Compound A40-10 (352.6 mg, 0.68 mmol), 3-methyl-3,9-diazaspiro[5,5]undecane (231.5 mg, 1.37 mmol), methanesulfonic acid (2-dicyclohexylphosphine)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium (II) (96.7 mg, 0.11 mmol), dioxane (5 mL), LiHDMS (3.0 mL, 3.00 mmol, 1 M) were mixed evenly, protected by nitrogen, reacted at 60 ° C for 30 min, and concentrated under reduced pressure. The residue was prepared and separated by Prep-HPLC using a chromatographic column luna C18, 30*250mm, mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile from 17% to 50%, 20 mins), freeze-dried to obtain compound A40 (17.5 mg, 0.029 mmol, yield: 4.3%). MS: 603.29 [M+H] +

[0849] The following final product was prepared in a similar manner to Example 40

[0850] Example 42 Synthesis of Compound A42

[0851] 2 6 -Amino-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0852] Step 1: Synthesis of Compound A42

[0853] Compound A40 (50 mg, 0.083 mmol), ammonium chloride (13.3 mg, 0.25 mmol), Pd2(dba)3 (15.2 mg, 0.02 mmol), xantPhos (9.61 mg, 0.02 mmol), and sodium tert-butoxide (39.83 mg, 0.41 mmol) were added to 1,4-dioxane (6 mL) and the reaction temperature was raised to 110°C under N2 protection. After 8 hours, the starting material disappeared, and the reaction was stopped. The mixture was concentrated under reduced pressure, and the residue was subjected to preparative HPLC separation using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 mins) to obtain compound A42 (8.7 mg, 18% yield). MS: 584.34 [M+H] +

[0854] Example 43 Synthesis of Compound A43

[0855] 2 6 -ethynyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0856] Step 1: Synthesis of compound A43-1

[0857] Compound A40 (50 mg, 0.083 mmol), trimethylsilylacetylene (41 mg, 0.414 mmol), tetrakistriphenylphosphine palladium (10 mg, 0.008 mmol), cuprous iodide (6 mg, 0.033 mmol), and N,N-diisopropylethylamine (32 mg, 0.249 mmol) were dissolved in 1,4-dioxane (8 mL) and the reaction was heated to 120°C under nitrogen protection. After 16 hours, the starting material disappeared, and the reaction was stopped. The reaction was concentrated under reduced pressure, and the residue was subjected to preparative HPLC separation using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins) to obtain compound A43-1 (48 mg, 0.072 mmol, yield: 87.0%). MS: 665.38 [M+H] +

[0858] Step 2: Synthesis of compound A43

[0859] Compound A43-1 (48 mg, 0.072 mmol) and potassium carbonate (50 mg, 0.36 mmol) were dissolved in methanol (8 mL) and stirred at room temperature for 0.5 hour. The starting material disappeared, the reaction was stopped, and the mixture was concentrated under reduced pressure. The residue was subjected to preparative HPLC separation using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 mins). The mixture was then lyophilized to obtain compound A43 (20 mg, 0.034 mmol, yield: 46.9%). MS: 593.36 [M+H] +

[0860] Example 44 Synthesis of Compound A44

[0861] 2 6 -ethyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0862] Step 1: Synthesis of compound A44

[0863] Compound A40 (50 mg, 0.083 mmol) and Pd(dppf)Cl2 (6 mg, 0.008 mmol) were dissolved in anhydrous 1,4-dioxane (6 mL). Diethylzinc (1 M in n-hexane, 0.08 mL) was slowly added. The reaction was heated to 60°C under nitrogen protection. After 16 hours, the starting material disappeared, and the reaction was stopped. The mixture was concentrated under reduced pressure, and the residue was subjected to preparative HPLC separation using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 mins) to obtain compound A44 (12 mg, 0.02 mmol, yield: 24.2%). MS: 597.38 [M+H] +

[0864] Example 37 Synthesis of Compound A37

[0865] 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrimidin-1(4,5)-pyrazolocycloundecyl-3-one

[0866] Step 1: Synthesis of compound A37-2

[0867] Compound A40-3 (1.16 g, 3.25 mmol) was added to ACN (25 mL), followed by A37-1 (1.52 g, 8.14 mmol), B2Pin2 (2.07 g, 8.14 mmol), Pd(Amphos)2Cl2 (0.23 g, 0.33 mmol), sodium carbonate (0.86 g, 8.14 mmol), and water (5 mL). The atmosphere in the reaction system was replaced with nitrogen three times, and the reaction was carried out under a nitrogen balloon at 100°C for 8 hours. The reaction was monitored for completion by LCMS. The reaction was cooled to room temperature, and 100 mL of water was added. The pH was adjusted to 4 with 2N HCl. The product was extracted with ethyl acetate (100 mL x 2), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography (DCM:MeOH = 10:1) to obtain compound A37-2 (0.58 g, 48.9% yield). MS:365.16[M+H] +

[0868] Step 2: Synthesis of compound A37-3

[0869] A37-2 (0.4 g, 1.10 mmol) and methanol (10 mL) were added to a reaction flask, cooled to 0-5°C, and concentrated sulfuric acid (0.5 mL) was slowly added. After addition was complete, the temperature was raised to 70°C and the reaction was allowed to proceed for 1.5 h. The reaction was monitored by LCMS. The mixture was concentrated, 20 mL of water was added, and the pH was adjusted to >9 with potassium carbonate. The mixture was extracted with DCM (20 mL x 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the product A37-3 (135 mg, yield: 49.6%). MS: 249.09 [M+H] +

[0870] Step 3: Synthesis of compound A37-4

[0871] The synthesis method of compound A37-4 is the same as that of compound A02-4, except that compound A02-1 is replaced by compound A37-3. MS of compound A37-4: 533.11, 535.11 [M+H] +

[0872] Step 4: Synthesis of compound A37-5

[0873] The synthesis method of compound A37-5 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A37-4. MS of compound A37-5: 503.13, 505.13 [M+H] +

[0874] Step 5: Synthesis of compound A37-6

[0875] The synthesis method of compound A37-6 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A37-5. MS of compound A37-6: 528.13, 530.13 [M+H] +

[0876] Step 6: Synthesis of Compound A37-7

[0877] The synthesis method of compound A37-7 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A37-6. MS of compound A37-7: 514.11, 516.11 [M+H] +

[0878] Step 7: Synthesis of Compound A37-8

[0879] The synthesis method of compound A37-8 is the same as that of compound A02-8, except that compound A02-7 is replaced by compound A37-7. MS of compound A37-8: 496.10, 498.10 [M+H] +

[0880] Step 8: Synthesis of Compound A37

[0881] The synthesis method of compound A37 is the same as that of compound A02, except that 2-methyl-2,7-diazaspiro[3.5]nonane is replaced by 3-methyl-3,9-diazaspiro[5,5]undecane, and compound A02-8 is replaced by A37-8. MS of compound A37: 584.34 [M+H] +

[0882] Example 52 Synthesis of Compound A52

[0883] (R)-1 1 , 2 6 ,7-trimethyl-56 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one

[0884] Step 1: Synthesis of compound A52-1

[0885] (R)-3,7-Dimethyloct-6-enoic acid (1.45 g, 10 mmol), tert-amyl alcohol (10 mL), DPPA (2.5 g, 10 mmol), and triethylamine (5 g, 20 mmol) were mixed and reacted at 100°C for 3 h. The starting material disappeared after TLC monitoring. The mixture was cooled to room temperature, and 30 mL of water was added. The mixture was extracted with ethyl acetate (3 x 15 mL). The organic phase was dried and then chromatographed using a PE / EA ratio of 5 / 1 to obtain compound A52-1 (1.20 g, yield: 45%). MS: 256.22 [M+H] +

[0886] Step 2: Synthesis of compound A52-2

[0887] Compound A52-1 (1.20 g, 4.71 mmol) was dissolved in THF (10 mL), and potassium tert-butoxide (10 mL, 1 M) was added. The mixture was reacted at 90°C for 2 h. The reaction solution was poured into 50 mL of water and extracted with 3 x 30 mL of ethyl acetate. The mixture was dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation. The mixture was used directly in the next step. The crude product (0.72 g, yield: 99%) was obtained. MS: 142.15 [M+H] +

[0888] Step 3: Synthesis of compound A52-3

[0889] The synthesis method of compound A52-3 is the same as that of compound A02-2, except that 5-aminopentan-1-ol is replaced by compound A52-2. MS of compound A52-3: 341.08, 343.08 [M+H] +

[0890] Step 4: Synthesis of compound A52-4

[0891] Compound A52-3 (0.50 g, 1.47 mmol) was dissolved in DCM (10 mL), and m-chloroperbenzoic acid (296 mg, 1.47 mg, 85%) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was complete after LCMS monitoring. 10 mL of saturated sodium sulfite and 10 mL of saturated sodium carbonate solution were added, and the mixture was separated. The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give a crude product (520 mg, yield: 99%). MS: 357.07, 359.07 [M+H] +

[0892] Step 5: Synthesis of compound A52-5

[0893] Compound A52-4 (0.52 g, 1.46 mmol) was dissolved in THF (10 mL) and periodic acid (333 mg, 1.47 mg) was added. The mixture was allowed to react at room temperature for 1 h. The reaction was monitored by LCMS for completion. 20 mL of saturated sodium carbonate solution was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The mixture was dried by spin chromatography using a PE / EA (1 / 1) column to obtain compound A52-5 (460 mg, yield: 99%). MS: 315.03, 317.03 [M+H] +

[0894] Step 6: Synthesis of Compound A52-6

[0895] Compound A52-5 (0.46 mg, 1.46 mmol) was dissolved in MeOH (10 mL), and sodium borohydride (55 mg, 1.46 mmol) was added at 0°C. The reaction was allowed to react for 1 h at 0°C. LCMS monitored the reaction to completion. 20 mL of saturated ammonium chloride solution was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The mixture was spin-dried and then column chromatography (PE / EA = 1 / 1) was performed to obtain compound A52-6 (443 mg, yield: 96%). MS: 317.04, 319.04 [M+H] +

[0896] Step 7: Synthesis of Compound A52-7

[0897] The synthesis method of compound A52-7 is the same as that of compound A02-3, except that compound A02-2 is replaced by compound A52-6. MS of compound A52-7: 395.02 [M+H] +

[0898] Step 8: Synthesis of Compound A52-8

[0899] The synthesis method of compound A52-8 is the same as that of compound A02-4, except that compound A02-3 is replaced by compound A52-7. MS of compound A52-8: 546.13, 548.13 [M+H] +

[0900] Step 9: Synthesis of Compound A52-9

[0901] The synthesis method of compound A52-9 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A52-8. MS of compound A52-9: 516.15, 518.15 [M+H] +

[0902] Step 10: Synthesis of Compound A52-10

[0903] The synthesis method of compound A52-10 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A52-9. MS of compound A52-10: 541.15, 543.15 [M+H] +

[0904] Step 11: Synthesis of Compound A52-11

[0905] The synthesis method of compound A52-11 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A52-10. MS of compound A52-11: 527.13, 529.13 [M+H] +

[0906] Step 12: Synthesis of Compound A52-12

[0907] The synthesis method of compound A52-12 is the same as that of compound A02-8, except that compound A02-7 is replaced by compound A52-11. MS of compound A52-12: 509.12, 511.12 [M+H] +

[0908] Step 13: Synthesis of Compound A52

[0909] The synthesis method of compound A52 is the same as that of compound A03-9, except that compound A03-7 is replaced by compound A52-12, and compound A03-8 is replaced by compound A52-13. MS of compound A52: 597.37 [M+H]+

[0910] Example 15 Synthesis of Compound A15

[0911] 1 1 , 2 6 -Dimethyl-5- 6 -(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1 1 H, 5 1 H-11-oxa-4,6-diaza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3,7-dione

[0912] Step 1: Synthesis of compound A15-3

[0913] Compound A02-1 (2.48 g, 10 mmol) was added to a reaction flask at room temperature, followed by DMF (25 mL), potassium carbonate (4.15 g, 30 mmol), and potassium iodide (1.66 g, 10 mmol). Finally, compound A15-2 (2.67 g, 12 mmol) was added and stirred at room temperature for 18 hours. The reaction was monitored by LCMS. After stopping, the reaction system was poured into water (100 mL) and stirred for 10 minutes. Ethyl acetate (250 mL) was added for extraction, the layers were separated, and the organic phase was removed by rotary evaporation. Silica gel was added and the sample was passed through a column. The eluent was changed from pure PE to PE:EA = 1:1. Concentration afforded the product (3.5 g, yield: 90%), MS: 390.20 [M+H]. +

[0914] Step 2: Synthesis of compound A15-4

[0915] Compound A15-3 (3.5 g, 9 mmol) was added to a reaction flask, followed by methanol (35 mL) as solvent. A hydrochloric acid / dioxane solution (9 mL, 4 M) was added dropwise at 0°C, and the mixture was stirred at room temperature for 2 hours. The reaction was monitored by LCMS. After stopping the reaction, the solvent was removed by rotary evaporation to obtain 2.5 g of the crude product (yield: 83%). MS: 334.13 [M+H] +

[0916] Step 3: Synthesis of compound A15-6

[0917] Compound A15-4 (2.5 g, 7.5 mmol) was added to a reaction flask, followed by DMF (25 mL) as solvent, HATU (3.81 g, 8 mmol) and A15-5 (1.85 g, 8 mmol), and finally DIPEA (2.83 g, 22 mmol). The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the reaction solution was poured into stirred water (100 mL) and stirred for 10 minutes. Ethyl acetate (250 mL) was added for extraction, dried, and the sample was added to a silica gel column. The eluent was then rinsed with pure PE and then pure EA. The product was concentrated to obtain 3.5 g (yield: 85%). MS: 547.09, 549.09 [M+H] +

[0918] Step 4: Synthesis of Compound A15-7

[0919] Compound A15-6 (3.5 g, 6.4 mmol) was added to a reaction flask, followed by methanol (30 mL) and water (5 mL). Iron powder (1.79 g, 32 mmol) and ammonium chloride (1.73 g, 32 mmol) were then added and the mixture was allowed to react at 60°C for 3 hours. LCMS was used to monitor the reaction. Heating was stopped, and silica gel was added to the sample and passed through a column. The eluent was changed from pure PE to pure EA. Concentration afforded 3 g of the product (yield: 91%). MS: 517.11, 519.11 [M+H] +

[0920] Step 5: Synthesis of Compound A15-8

[0921] Compound A15-7 (3 g, 5.8 mmol) was added to a reaction flask, followed by methanol (35 mL) and water (5 mL). Cyanogen bromide (795 mg, 7.5 mmol) was then added and the reaction was allowed to proceed at 60°C for 3 hours. The reaction was monitored by LCMS. Heating was discontinued, and the reaction mixture was mixed with silica gel and passed through a column using eluents ranging from pure PE to pure EA. The column was concentrated to yield 2.8 g of the product (yield: 89%). MS: 542.11, 544.11 [M+H] +

[0922] Step 6: Synthesis of Compound A15-9

[0923] Compound A15-8 (2.8 g, 5.2 mmol) was added to a reaction flask, followed by methanol (25 mL) and water (5 mL). Lithium hydroxide (625 mg, 26 mmol) was then added as a base and stirred at room temperature for 2 hours. The reaction was monitored by LCMS. The reaction was stopped and 2N hydrochloric acid was added dropwise at 0°C to adjust the pH to 5. Solids precipitated and the mixture was stirred for 10 minutes. The mixture was filtered to obtain 2.23 g of the product (yield: 81%). MS: 528.09, 530.09 [M+H] +

[0924] Step 7: Synthesis of Compound A15-10

[0925] Compound A15-9 (2.23 g, 4.23 mmol) was added to a reaction flask, followed by dichloromethane (25 mL) solvent, pyridine (1.19 g, 15 mmol) and phosphorus oxychloride (765 mg, 5 mmol), and the mixture was stirred at room temperature for 2 hours. The reaction was monitored by LCMS. After stopping the reaction, the reaction solution was added dropwise to water (100 mL) and stirred for 10 minutes. Dichloromethane (250 mL) was added for extraction and separation. The mixture was dried, and silica gel was added to the sample and passed through a column. The eluent was then rinsed with pure PE and then pure EA. Concentration afforded 1.8 g of the product (yield: 79%). MS: 510.08, 512.08 [M+H] +

[0926] Step 8: Synthesis of Compound A15

[0927] Compound A15-10 (509 mg, 1 mmol) was added to a reaction flask, followed by dioxane (5 mL) and water (1 mL). Compound A15-11 (335 mg, 1.5 mmol), potassium carbonate (415 mg, 3 mmol), and Pd(dppf)Cl2 (73.1 mg, 0.1 mmol) were then added. The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added and passed through a column using a mixture of pure PE and EA as the eluent. The crude product was concentrated and then subjected to Prep-HPLC using a Luna C18, 30 x 250 mm column and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). The preparative solution was evaporated to remove most of the organic solvent and then lyophilized to afford 80 mg of the product (yield: 15%). MS: 527.24 [M+H] +

[0928] Example 58 Synthesis of Compound A58

[0929] (Z)-2 6 -methyl-5 6-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 , 1 5 , 1 6 , 1 7 -Tetrahydro-5- 1 H-4-Aza-1(3,5)-[1,2,3]triazolo[1,5-a]pyrazine-5(2,1)-benzo[d]imidazo-2(2,4)-pyridinylcyclononane-3-one

[0930] Step 1 Synthesis of Compound A58-2

[0931] Compound A58-1 (2 g, 6.60 mmol), B2Pin2 (2.51 g, 9.90 mmol), Pd(dppf)Cl2 (0.48 g, 0.66 mmol), potassium acetate (1.29 g, 13.19 mmol), and dioxane (30 mL) were mixed uniformly and reacted at 100°C for 5 h under nitrogen atmosphere. The mixture was filtered, concentrated, and purified by column chromatography (PE:EA = 3:1) to give compound A58-2 (1.18 g, 51.1% yield). MS: 351.21 [M+H] +

[0932] Step 2 Synthesis of Compound A58-4

[0933] The synthesis method of compound A58-4 is the same as that of A40-4, except that compound A40-1 is replaced by A58-2, and A40-3 is replaced by A58-3. MS of compound A58-4: 374.18 [M+H] +

[0934] Step 3 Synthesis of Compound A58-5

[0935] The synthesis method of compound A58-5 is the same as that of A03-10, except that compound A03-9 is replaced by A58-4. MS of compound A58-5: 274.12 [M+H] +

[0936] Step 4: Synthesis of Compound A58-7

[0937] The synthesis method of compound A58-7 is the same as that of A02, except that compound A02-8 is replaced by A58-6 and 2-methyl-2,7-diazaspiro[3.5]nonane is replaced by A58-5. MS of compound A58-7: 445.25 [M+H] +

[0938] Step 5 Synthesis of Compound A58-8

[0939] The synthesis method of compound A58-8 is the same as that of A58-5, except that compound A58-4 is replaced by A58-7. MS of compound A58-8: 345.20 [M+H] +

[0940] Step 6 Synthesis of Compound A58-9

[0941] The synthesis method of compound A58-9 is the same as that of A02-2, except that compound 5-aminopentan-1-ol is replaced by A58-8. MS of compound A58-9: 544.12, 546.12 [M+H] +

[0942] Step 7 Synthesis of Compound A58-10

[0943] The synthesis method of compound A58-10 is the same as that of A02-5, except that compound A02-4 is replaced by A58-9. MS of compound A58-10: 514.15, 516.15 [M+H] +

[0944] Step 8: Synthesis of Compound A58-11

[0945] The synthesis method of compound A58-11 is the same as that of A02-6, except that compound A02-5 is replaced by A58-10. MS of compound A58-11: 539.14, 541.14 [M+H] +

[0946] Step 9: Synthesis of Compound A58-12

[0947] The synthesis method of compound A58-12 is the same as that of A02-7, except that compound A02-6 is replaced by A58-11. MS of compound A58-12: 525.13, 527.13 [M+H] +

[0948] Step 10: Synthesis of Compound A58-13

[0949] The synthesis method of compound A58-13 is the same as that of A02-8, except that compound A02-7 is replaced by A58-12. MS of compound A58-12: 507.12, 509.12 [M+H] +

[0950] Step 11: Synthesis of Compound A58

[0951] The synthesis method of compound A58 is the same as that of compound A02, except that 2-methyl-2,7-diazaspiro[3.5]nonane is replaced by 3-methyl-3,9-diazaspiro[5,5]undecane, and compound A02-8 is replaced by A58-13. MS of compound A58: 595.35 [M+H] +

[0952] Example 59 Synthesis of Compound A59

[0953] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 H, 5 1 H-4-Aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(3,4)-triazolocycloundecyl-3-one

[0954] Step 1: Synthesis of compound A59-3

[0955] Compound A59-2 (11 g, 50 mmol) was added to a reaction flask, followed by DMF (110 mL) and potassium carbonate (20.7 g, 150 mmol), followed by compound A59-1 (10.7 g, 50 mmol), and the mixture was stirred at room temperature for 3 hours. LCMS was used to monitor the reaction. Upon completion, the reaction solution was poured into water (300 mL), stirred for 10 minutes, and extracted with ethyl acetate (1000 mL). The mixture was dried and the solvent removed by rotary evaporation to obtain 19 g of the product (yield: 92%). MS: 416.11, 418.11 [M+H] +

[0956] Step 2: Synthesis of compound A59-4

[0957] The synthesis method of compound A59-4 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A59-3. MS of compound A59-4: 386.14, 388.14 [M+H] +

[0958] Step 3: Synthesis of compound A59-5

[0959] Compound A59-4 (15 g, 39 mmol) was added to a reaction flask, followed by methanol (1200 mL) and water (30 mL). Nitrile bromide (5.3 g, 50 mmol) was then added and allowed to react at 60°C for 2 hours. The reaction was monitored by LCMS. Upon completion, the sample was added to a silica gel column and flushed with eluents ranging from pure PE to pure EA. The product (10 g, yield: 63%) was obtained by concentration. MS: 411.13, 413.13 [M+H] +

[0960] Step 4: Synthesis of compound A59-7

[0961] Compound A59-5 (10 g, 24.3 mmol) was added to a reaction flask, followed by DMF (100 mL) as solvent, HATU (9.5 g, 25 mmol) and A59-6 (4.53 g, 25 mmol), and finally DIPEA (9.68 g, 75 mmol). The reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. After stopping the reaction, the reaction solution was poured into stirred water (300 mL) and stirred for 10 minutes. Ethyl acetate (1000 mL) was added for extraction and separation. The mixture was dried, mixed with silica gel, and passed through a column. The eluent was then rinsed with pure PE and then pure EA. Concentration afforded 12 g of the product (yield: 86%). MS: 574.16, 576.16 [M+H] +

[0962] Step 5: Synthesis of compound A59-8

[0963] Compound A59-7 (12 g, 20.9 mmol) was added to a reaction flask, followed by methanol (120 mL) and hydrazine hydrate (2.1 g, 20.9 mmol). The reaction was allowed to react at 60°C for 5 hours. LCMS was used to monitor the reaction. Upon completion, the solvent was removed by rotary evaporation, and the sample was mixed with silica gel and passed through a column. The eluent was then rinsed with pure PE and then pure EA. Concentration afforded 9 g of the product (yield: 75%). MS: 574.17, 576.17 [M+H] +

[0964] Step 6: Synthesis of Compound A59-9

[0965] Compound A59-8 (9 g, 15.7 mmol) was added to a reaction flask, followed by methanol (90 mL). Dioxane hydrochloride (16 mL, 4 M) was added dropwise at 0°C and stirred at room temperature for 2 hours. LCMS was used to monitor the reaction. Upon completion, the solvent was removed by rotary evaporation to obtain 5 g of the product (yield: 67%). MS: 474.12, 476.12 [M+H] +

[0966] Step 7: Synthesis of Compound A59-10

[0967] Compound A59-9 (5 g, 10.6 mmol) was added to a reaction flask, followed by toluene (50 mL), acetic acid (2 mL), and N,N-dimethylformamide dipropyl acetal (3 mL). The reaction was refluxed for 3 hours. LCMS was used to monitor the reaction. After stopping the reaction, heating was performed and the solvent was removed by rotary evaporation. Silica gel was added to the sample and the column was passed through. The eluent was changed from pure PE to pure EA. Concentration afforded 3 g of the product (yield: 59%). MS: 480.11, 482.11 [M+H] +

[0968] Step 8: Synthesis of Compound A59

[0969] Compound A59-10 (479 mg, 1.0 mmol) was added to a reaction flask, followed by dioxane (5.0 mL) as solvent. Sodium tert-butoxide (290 mg, 3.0 mmol), BINAP (62.3 mg, 0.1 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), and 3-methyl-3,9-diazaspiro[5,5]undecane (252 mg, 1.5 mmol) were then added. The atmosphere was purged with nitrogen and the reaction was carried out at 90°C for 3 hours. The reaction was monitored by LCMS. Heating was stopped, and the sample was added with silica gel and passed through a column. The eluent was then rinsed with pure PE and then pure EA. Concentration afforded 190 mg of the product (yield: 33.5%). MS: 568.34 [M+H] +

[0970] Example 60 Synthesis of Compound A60

[0971] (1 3 Z, 1 4 E, 5 2 Z)-2 6 -methyl-5 6 -((4-methylpiperazin-1-yl)methyl)-5-(4-methylpiperazin-1-yl)methyl)- 2 , 5 3 -Dihydro-5 1 H-9-oxa-4-aza-1(3,5),5(2,1)-dipyrazolo[1,5-a]pyrido-2(2,4)-pyridocyclononane-3-one

[0972] Step 1: Synthesis of compound A60-1

[0973] Pyrazolo[1,5-A]pyridin-5-ol (1.34 g, 9.99 mmol) was added to DMF (20.00 mL), followed by N-Boc-3-aminopropyl bromide (2.62 g, 10.99 mmol) and potassium carbonate (4.14 g, 29.97 mmol). After the addition was complete, the mixture was heated to 70°C and reacted for 3 hours. LCMS monitoring was performed and the temperature was lowered after the reaction was complete. The reaction solution was poured into 100 mL of water and extracted with EA (50 mL x 3). The organic phases were combined and washed with saturated brine. The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (PE / EA = 2 / 1) to obtain compound A60-1 (2.5 g, yield: 85.9%). MS: 292.16 [M+H] + .

[0974] Step 2: Synthesis of compound A60-2

[0975] Compound A60-1 (2.50 g, 8.58 mmol) was added to DCM / dichloromethane (30.00 mL), followed by the addition of NBS (2.29 g, 12.87 mmol). The reaction was stirred at room temperature overnight. LCMS monitored the reaction for completion. The product was washed with water, concentrated, and purified by column chromatography (PE / EA = 1 / 1) to afford product A60-2 (2.8 g, yield: 88%). MS: 370.11, 372.11 [M+H] +

[0976] Step 3: Synthesis of compound A60-3

[0977] Compound A60-2 (2.80 g, 7.56 mmol) was added to dioxane (50 mL), followed by bis(boronic acid) pinacol ester (5.76 g, 22.68 mmol), [PdCl2(dppf)]CH2Cl2 (0.616 g, 0.76 mmol), and KOAc (2.23 g, 22.68 mmol). After the addition was complete, the atmosphere was replaced with nitrogen three times. Under nitrogen, the reaction mixture was heated to 80°C for 3 hours. The reaction was stopped, the temperature was lowered, and the mixture was concentrated. The residue was purified by column chromatography (PE / EA = 3 / 1) to afford product A60-3 (1.3 g, 41% yield), MS: 418.24 [M+H] +

[0978] Step 4: Synthesis of compound A60-4

[0979] Compound A60-3 (1.2 g, 2.85 mmol) was added to dioxane (20 mL), followed by methyl 2-chloro-6-methylisonicotinate (0.79 g, 4.27 mmol), [PdCl2(dppf)]CH2Cl2 (0.234 g, 0.29 mmol), potassium carbonate (1.12 g, 8.55 mmol), and H2O (2 mL). After the addition was complete, the atmosphere was replaced with nitrogen three times. Under nitrogen protection, the mixture was heated to 100°C for 3 hours. The reaction was stopped, the temperature was lowered, and the mixture was concentrated. The residue was purified by column chromatography (PE / EA = 1 / 1) to obtain product A60-4 (0.94 g, yield: 75%), MS: 441.22 [M+H] +

[0980] Step 5: Synthesis of compound A60-5

[0981] Compound A60-4 (900 mg, 2.05 mmol) was added to DCM (20 mL), followed by a 4 M solution of dioxane hydrochloride (2 mL). After the addition was complete, the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until complete. The reaction was stopped, filtered, and the filter cake was rinsed with DCM to obtain product A60-5 (0.77 g, yield: 100%). MS: 341.15 [M+H] +

[0982] Step 6: Synthesis of Compound A60-6

[0983] The synthesis method is the same as A60-1, except that the raw materials are replaced with A60-5 and 2-fluoro-4-bromonitrobenzene. The product A60-6 is obtained, MS: 540.08, 542.08 [M+H] +

[0984] Step 7: Synthesis of Compound A60-7

[0985] Compound A60-6 (900 mg, 1.67 mmol) was added to MeOH (3 mL), followed by DCM (3 mL) and stirred to dissolve. A saturated aqueous solution of ammonium chloride (6 mL) was then added. With stirring, Zn powder (1.08 g, 16.7 mmol) was added portionwise and the mixture was stirred at room temperature for 1 hour. LCMS was used to monitor the reaction until completion. 10 mL of DCM and 10 mL of water were added, the layers were separated, and the organic phase was washed with saturated brine and concentrated to afford product A60-7 (807 mg, yield: 95%). MS: 510.10, 512.10 [M+H] +

[0986] Step 8: Synthesis of Compound A60-8

[0987] Compound A60-7 (800 mg, 1.57 mmol) was added to MeOH (5 mL), followed by H2O (5 mL). After stirring, BrCN (0.25 g, 2.34 mmol) was added and the mixture was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion. 10 mL of DCM and 10 mL of water were added, the layers were separated, and the organic phase was washed with saturated brine and concentrated to afford product A60-8 (754 mg, yield: 90%). MS: 535.11, 537.11 [M+H] +

[0988] Step 9: Synthesis of compound A60-9

[0989] Compound A60-8 (750 mg, 1.40 mmol) was added to MeOH (5 mL), followed by 6N aqueous NaOH (5 mL), and the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion, after which the majority of the methanol was removed by concentration. The remaining system was adjusted to pH 6-7 with 1N aqueous hydrochloric acid and extracted with DCM (20 mL x 5). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to afford product A60-9 (613 mg, 84% yield). MS: 521.10, 523.10 [M+H] +

[0990] Step 10: Synthesis of Compound A60-10

[0991] Compound A60-9 (300 mg, 0.58 mmol) was added to DMF (5 mL) and the temperature was lowered to 0°C. HATU (220.57 mg, 0.58 mmol) was added portionwise. After the addition was complete, the mixture was maintained at 0°C and stirred for 1 hour. The reaction was monitored by LCMS until completion. The reaction was stopped and the reaction solution was poured into 30 mL of water and extracted with DCM (20 mL x 3). The organic phases were combined and concentrated, and the residue was purified by reverse phase column chromatography (H2O / ACN = 0-60%) to obtain product A60-10 (137 mg, yield: 47%). MS: 503.09, 505.09 [M+H] +

[0992] Step 11: Synthesis of Compound A60

[0993] Compound A60-10 (100 mg, 0.2 mmol) was added to dioxane (5 mL), followed by potassium 1-methyl-4-trifluoroborate trimethylpiperazine (220 mg, 1 mmol), Pd(dba) (29.3 mg, 0.03 mmol), Xphos (23.8 mg, 0.05 mmol), KCO (82.8 mg, 0.6 mmol), and water (0.5 mL). After addition, the atmosphere was purged with nitrogen three times. The temperature was raised to 100°C and the reaction was allowed to react for 2 h. LCMS was used to monitor the reaction until completion. The mixture was diluted with 20 mL of DCM and washed with saturated brine. The organic phase was concentrated. The residue was purified by prep-HPLC using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% in 20 mins) and lyophilized to afford product A60 (22 mg, yield: 21%), MS: 537.26 [M+H] +

[0994] Example 64 Synthesis of Compound A64

[0995] 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-4-Aza-5(2,1)-benzo[d]imidazo-1(7,1)-imidazo[1,2-b]pyrazol-2(2,4)-pyridocyclodecane-3-one

[0996] Step 1 to Step 10 Synthesis of Compounds A64-1 to A64-10

[0997] The synthetic route of compounds A64-1 to A64-10 is the same as that of A60-1 to A60-10, except that the starting materials are replaced with 1H-imidazo[1,2-B]pyrazole and 5-(tert-butoxycarbonylamino)bromopentane. Product A64-10, MS = 504.11, 506.11

[0998] Step 11 Synthesis of Compound A64-11

[0999] The synthesis method of compound A64-11 is the same as that of A18-1, except that the starting material is replaced with A64-10. The product A64-11 is obtained, MS: 634.19, 636.19 [M+H] +

[1000] Step 12: Synthesis of Compound A64-12

[1001] The synthesis method of compound A64-12 is the same as that of A18-2, except that the starting material is replaced with A64-11. The product A64-12 is obtained, MS: 722.43 [M+H] +

[1002] Step 13: Synthesis of Compound A64

[1003] The synthesis method of compound A64 is the same as that of A18, except that the starting material is replaced with A64-12. The product A64 is obtained, MS: 592.35 [M+H] +

[1004] The following final products were prepared in a similar manner to Examples 58, 59, 60 and 64.

[1005] Example 68 Synthesis of Compound A68

[1006] 3 6 -methyl-6 6 -((4-methylpiperazin-1-yl)methyl)-6- 1 H-11-oxa-2,5-diaza-6(2,1)-benzo[d]imidazol-1,3(2,4)-bipyridocycloundecyl-4-one

[1007] Step 1: Synthesis of compound A68-1

[1008] 2-Fluoro-4-bromonitrobenzene (2.2 g, 10 mmol) was added to DMF (20.00 mL), followed by 4-amino-1-butanol (1.07 g, 12 mmol) and potassium carbonate (4.14 g, 29.97 mmol). After the addition was complete, the reaction was stirred at room temperature overnight. LCMS was used to monitor the reaction until completion. The reaction solution was poured into 100 mL of water. The precipitated solid was filtered, and the filter cake was rinsed with water and dried to obtain the product, compound A68-1 (2.6 g, yield: 90%). MS: 289.01, 291.01 [M+H] + .

[1009] Step 2: Synthesis of compound A68-2

[1010] A68-1 (2.6 g, 9.02 mmol) was added to DCM / dichloromethane (30.00 mL), followed by triethylamine (2.74 g, 27.10 mmol). The temperature was lowered to 0°C, and MsCl (2.07 g, 18.04 mmol) was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours. LCMS monitored the reaction completion. The organic phase was washed with water and concentrated to afford the product A68-2 (3.07 g, 93% yield). MS: 366.99, 368.99 [M+H] +

[1011] Step 3: Synthesis of compound A68-3

[1012] Methyl 2-chloro-6-methylisonicotinate (1.85 g, 10 mmol) was added to dioxane (20 mL), followed by 4-(benzyloxy)pyridin-2-amine (2 g, 10 mmol), brettphos Pd G3 (1.81 g, 1.99 mmol), and K2CO3 (4.13 g, 29.9 mmol). After the addition was complete, the atmosphere was replaced with nitrogen three times. Under nitrogen protection, the reaction was heated to 100°C for 3 hours. LCMS monitoring was performed until the reaction was completely stopped, the temperature was lowered, and the reaction was concentrated. The residue was purified by column chromatography (PE / EA = 1 / 1) to obtain product A68-3 (1.1 g, yield: 32%), MS: 350.14 [M+H] +

[1013] Step 4: Synthesis of compound A68-4

[1014] A68-3 (1.1 g, 3.15 mmol) was added to tetrahydrofuran (20 mL), followed by (Boc)2O (1.37 g, 6.30 mmol), DIEA (1.22 g, 9.54 mmol), and DMAP (76.93 mg, 0.63 mmol). After the addition was complete, the mixture was heated to 70°C and reacted for 3 hours. After completion of the reaction, the reaction was stopped, cooled, and concentrated. The residue was purified by column chromatography (PE / EA = 2 / 1) to afford A68-4 (1.1 g, 77% yield), MS: 450.20 [M+H] +

[1015] Step 5: Synthesis of compound A68-5

[1016] A68-4 (1.1 g, 2.45 mmol) was added to MeOH (10 mL), followed by 10% Pd / C (104 mg, 0.49 mmol). After the addition was complete, the atmosphere was replaced with hydrogen three times and the reaction was stirred at room temperature for 2 hours. LCMS was used to monitor the reaction until completion. The reaction was stopped, filtered, and the filter cake was rinsed with methanol. The filtrate was concentrated to afford the product A68-5 (0.76 g, yield: 86%), MS: 360.15 [M+H] +

[1017] Step 6: Synthesis of Compound A68-6

[1018] A68-2 (388 mg, 1.06 mmol) was added to DMF (5 mL), followed by A68-5 (380 mg, 1.06 mmol) and K2CO3 (292 mg, 2.11 mmol). After the addition was complete, the mixture was heated to 60°C and stirred for 6 hours. LCMS was used to monitor the reaction until completion. The reaction was stopped and the reaction solution was poured into 20 mL of water. The precipitated solid was filtered, the filter cake was rinsed with water, and dried to obtain the product A68-6 (550 mg, yield: 82%), MS: 630.15 / 632.15 [M+H] +

[1019] Step 7: Synthesis of Compound A68-7

[1020] The synthesis method of compound A68-7 is the same as that of A60-7, except that the raw material is replaced with A68-6. The product A68-7 is obtained, MS: 586.16 / 588.16 [M+H] +

[1021] Step 8: Synthesis of Compound A68-8

[1022] The synthesis method of compound A68-8 is the same as that of A60-8, except that the raw material is replaced with A68-7. The product A68-8 is obtained, MS: 625.17 / 627.17 [M+H] +

[1023] Step 9: Synthesis of Compound A68-9

[1024] The synthesis method of compound A68-9 is the same as that of A60-9, except that the starting material is replaced with A68-8. The product A68-9 is obtained, MS: 611.15 / 613.15 [M+H] +

[1025] Step 10: Synthesis of Compound A68-10

[1026] The synthesis method of compound A68-10 is the same as that of A60-10, except that the starting material is replaced with A68-9. The product A68-10 is obtained, MS: 593.14.15 / 595.14 [M+H] +

[1027] Step 11: Synthesis of Compound A68-11

[1028] Compound A68-10 (100 mg, 0.17 mmol) was added to dioxane (5 mL), followed by potassium 1-methyl-4-trifluoroborate trimethylpiperazine (220 mg, 1 mmol), Pd2(dba)3 (29.3 mg, 0.03 mmol), Xphos (23.8 mg, 0.05 mmol), K2CO3 (82.8 mg, 0.6 mmol), and water (0.5 mL). After the addition was complete, the atmosphere was purged with nitrogen three times. The temperature was raised to 100°C and the reaction was allowed to proceed for 2 h. LCMS was used to monitor the reaction until completion. The mixture was diluted with 20 mL of DCM and washed with saturated brine. The organic phase was concentrated to obtain crude product A68-11, MS: 627.33 [M+H]. +

[1029] Step 12: Synthesis of Compound A68

[1030] The crude product of compound A68-11 was added to DCM (5 mL) and stirred to dissolve. A 4N hydrochloric acid solution in dioxane (1 mL) was added dropwise. After completion of the addition, the reaction was stirred at room temperature for 2 hours. The reaction was monitored by LCMS until complete, concentrated, and the residue was purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 min) to obtain product A68 (28 mg). MS: 527.28 [M+H] +

[1031] The following final product was prepared according to the method of Example 68

[1032] Example 91 Synthesis of Compound A91

[1033] (E)-5 6 -(9-acetyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1034] Step 1: Synthesis of compound A91-1

[1035] The crude product of compound A13-1 was added to DCM (5 mL) and stirred to dissolve. A 4M hydrochloric acid solution in dioxane (1 mL) was added dropwise under an ice bath and the mixture was kept warm for 1 h. The reaction was monitored by LCMS for completion. The reaction solution was poured into 20 mL of saturated aqueous sodium carbonate solution, extracted with DCM, and dried by spin drying. The mixture was then passed through a reverse mobile phase (A: 0.05% F, water; B: ACN; gradient 0-75% B over 20 min). The product was dried by spin drying. MS: 699.41 [M+H]+

[1036] Step 2: Synthesis of compound A91-2

[1037] Compound A91-1 (30 mg, 0.04 mmol) and triethylamine (13 mg, 0.13 mmol) were added to DCM (5 mL) and stirred to dissolve. Acetyl chloride (4 mg, 0.05 mmol) was added under ice-cooling. LCMS monitored the reaction completion. The reaction solution was poured into 5 mL of saturated aqueous sodium carbonate solution, extracted with DCM, and dried to give the crude product. MS: 741.42 [M+H] +

[1038] Step 3: Synthesis of compound A91

[1039] Compound A91-2 (30 mg, 0.04 mmol) was added to DCM (3 mL). Trifluoroacetic acid (1 mL) was added under an ice bath and the mixture was allowed to react at room temperature for 2 h. LCMS monitored the reaction for completion. The product was then dried and 2 mL of acetonitrile was added, and the pH was adjusted to 7. The product was then prepared by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 15% to 50% over 20 mins) to obtain the product. MS: 611.34 [M+H] +

[1040] Example 212 Synthesis of Compound A212

[1041] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-(methylsulfonyl)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 51 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1042] Step 1: Synthesis of compound A212-1

[1043] Compound A91-1 (40 mg, 0.06 mmol), (methylsulfonyl)ethylene (18 mg, 0.17 mmol), and sodium carbonate (18 mg, 0.17 mmol) were added to 1,4-dioxane (5 mL) and MeOH (2 mL) and reacted at 70°C for 2 h. LCMS monitored the reaction completion. The reaction solution was poured into 10 mL of saturated aqueous sodium carbonate solution, extracted with DCM, and dried to give the crude product. MS: 805.42 [M+H] +

[1044] Step 2: Synthesis of compound A212

[1045] The synthesis method of compound A212 is the same as that of compound A91, except that the starting compound is replaced with compound A212-1. MS of compound A212: 675.34 [M+H] +

[1046] Example 92 Synthesis of Compound A92

[1047] (E)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1048] Step 1: Synthesis of compound A92-1

[1049] Compound A91-1 (30 mg, 0.04 mmol), 1-bromo-2-fluoroethane (13 mg, 0.13 mmol), and potassium carbonate (11.8 mg, 0.09 mmol) were added to ACN (5 mL). The mixture was reacted at 70°C for 12 h. LCMS monitored the reaction completion. The reaction solution was poured into 5 mL of saturated aqueous sodium carbonate solution, extracted with DCM, and dried to give the crude product. MS: 745.43 [M+H] +

[1050] Step 2: Synthesis of compound A92

[1051] The synthesis method of compound A92 is the same as that of compound A91, except that the starting compound is replaced with compound A92-1. MS of compound A92: 615.35 [M+H] +

[1052] Example 97 Synthesis of Compound A97

[1053] 1 1 ,2 6 -Dimethyl-5- 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-2-one

[1054] Step 1: Synthesis of compound A97

[1055] In a 50 mL single-necked vial, A13 (50 mg, 0.07 mmol) and tetrahydropyrone (14.32 mg, 0.14 mmol) were dissolved in dichloromethane (2 mL), mixed thoroughly, and reacted at 25°C for 2 h under a nitrogen atmosphere. Sodium triacetoxyborohydride (30.31 mg, 0.14 mmol) was added and the mixture was allowed to react at 25°C for 16 h. The starting material disappeared by TLC monitoring, then dried and dissolved in methanol. The product was then prepared by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 min) to afford compound A97 (10.2 mg, 0.016 mmol, 17.8% yield). MS: 653.38 [M+H] +

[1056] Example 118 Synthesis of Compound A118

[1057] (E)-1 1 ,2 6 -Dimethyl-5- 6 -(9-(1-methylpiperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 2 ,5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-2-one

[1058] Step 1: Synthesis of compound A118

[1059] In a 50 mL single-necked vial, A13 (50 mg, 0.07 mmol) and N-methyl-4-piperidone (49.73 mg, 0.44 mmol) were dissolved in dichloromethane (2 mL), mixed thoroughly, and reacted at 25°C for 2 h under a nitrogen atmosphere. Sodium triacetoxyborohydride (30.31 mg, 0.14 mmol) was added and the mixture was allowed to react at 25°C for 16 h. The starting material disappeared by TLC monitoring, then the product was dried by spin drying and dissolved in methanol. The product was then prepared by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 min) to afford compound A118 (1.9 mg, 0.016 mmol, 3.2% yield). MS: 666.42 [M+H] +

[1060] Example 121 Synthesis of Compound A121

[1061] 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1062] Step 1: Synthesis of compound A121

[1063] Compound A13 (40 mg, 0.07 mmol) was added to methanol (3 mL), followed by 3-methyl-3-azabicyclo[3.2.1]octan-8-one (48.7 mg, 0.35 mmol), sodium cyanoborohydride (83.67 mg, 1.33 mmol), and 2 drops of acetic acid. After the addition was complete, the mixture was heated to 60°C and allowed to react for 2 hours. The reaction was monitored by LCMS until complete, after which the product was concentrated and purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 mins) to afford product A121 (12.1 mg, 25% yield). MS: 692.43 [M+H] +

[1064] Example 124 Synthesis of Compound A124

[1065] 5 6 -(9-(4-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one

[1066] Step 1: Synthesis of compound A124

[1067] Compound A13 (40 mg, 0.07 mmol) and p-methoxycyclobutanone (27 mg, 0.21 mmol) were added to DCM (5 mL), and sodium acetate borohydride (45 mg, 0.21 mmol) was added at room temperature. The reaction was allowed to react at room temperature for 10 h. LCMS monitored the reaction completion. The product was then spin-dried and then subjected to Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 40% over 20 min) to obtain the product. MS: 681.42 [M+H] +

[1068] Example 125 Synthesis of Compound A125

[1069] 5 6 -(9-(4-hydroxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1070] Step 1: Synthesis of compound A125

[1071] A13 (30 mg, 0.05 mmol) was dissolved in methanol (2 mL). 4-Hydroxycyclohexanone (9 mg, 0.08 mmol), acetic acid (0.1 mL, 2 mmol), and sodium cyanoborohydride (7 mg, 0.1 mmol) were added sequentially in an ice-water bath. After completion, the mixture was stirred at room temperature for 2 days. LCMS was used to monitor the reaction until it was nearly complete. The product was then concentrated and purified by prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile concentration increased from 17% to 40% over 20 mins) to obtain product A125 (3.5 mg, 10% yield). MS: 667.40 [M+H] +

[1072] Example 128 Synthesis of Compound A128

[1073] 5 6 -(9-(8-oxabicyclo[3.2.1]octan-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1074] Step 1: Synthesis of compound A128

[1075] Compound A13 (56.8 mg, 0.1 mmol) was added to a reaction flask, and methanol (1 ml) was added as solvent. Acetic acid (0.1 mL) and compound A128-1 (63 mg, 0.5 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. Sodium cyanoborohydride (13 mg, 0.2 mmol) was added and stirred at 60°C for 1 hour. The temperature was lowered and the reaction solution was directly sent to Prep-HPLC for preparation. The chromatographic column was Luna C18, 30*250 mm, and the mobile phase was (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile was adjusted from 17% to 40% in 20 mins) to obtain the product compound A128 (13 mg, yield: 20%). MS: 679.39 [M+H]+

[1076] Example 129 Synthesis of Compound A129

[1077] 5 6 -(9-(2-hydroxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1078] Step 1: Synthesis of compound A129-2

[1079] A13 (120 mg, 0.21 mmol) was dissolved in dichloromethane (8 mL), and A129-1 (55 mg, 0.32 mmol), acetic acid (0.1 mL, 2 mmol), and sodium triacetoxyborohydride (89 mg, 0.42 mmol) were added sequentially under ice-water bath conditions. After the addition, the mixture was transferred to room temperature and stirred for 15 hours. The reaction was monitored by LCMS until it was almost complete. The mixture was concentrated and the residue was purified by PLC (DCM:MeOH=1:1) to obtain the product A129-2 (34 mg, yield: 22%).

[1080] Step 2: Synthesis of compound A129

[1081] A129-2 (34 mg, 0.05 mmol) was dissolved in dichloromethane (8 mL) and methanol (1 mL). A 4M HCl solution in 1,4-dioxane (0.5 mL) was added and stirred at room temperature for 1 hour. The reaction was monitored by LCMS until nearly complete. The product was concentrated and the residue was purified by PLC (DCM:MeOH = 8:1) to obtain product A129 (19 mg, yield: 66%). MS: 613.46 [M+H] +

[1082] Example 147 Synthesis of Compound A147

[1083] 5 6 -(9-(3-Hydroxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecane-3-one

[1084] Step 1: Synthesis of compound A147

[1085] A13 (120 mg, 0.21 mmol) was dissolved in methanol (8 mL). 3-Hydroxycyclobutanone (54 mg, 0.63 mmol), acetic acid (0.1 mL, 2 mmol), and sodium cyanoborohydride (27 mg, 0.42 mmol) were added sequentially in an ice-water bath. After the addition, the mixture was stirred at room temperature for 15 hours. LCMS was used to monitor the reaction until it was nearly complete. The mixture was concentrated and the residue was purified by PLC (DCM:MeOH = 8:1) to obtain product A147 (49 mg, yield: 29%). MS: 639.37 [M+H] +

[1086] The following final product was prepared in a similar manner to Example 147

[1087] Example 111 Synthesis of Compound A111

[1088] 1 1 , 2 6 -Dimethyl-5- 6 -(1'-methyl-3-azaspiro[bicyclo[3.2.1]octane-8,4'-piperidin]-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1089] Step 1: Synthesis of compound A111-1

[1090] Ethyl cyanoacetate (13.14 g, 116.12 mmol) was added to methanol (50 mL), cooled to 0°C, and ammonium acetate (5.37 g, 69.67 mmol), A111-0 (5.0 g, 23.22 mmol), and 25% aqueous ammonia (6.50 g, 46.45 mmol) were added. Stirring at room temperature for 30 minutes resulted in the precipitation of a large amount of white solid. Sodium hydroxide (6.50 g, 162.57 mmol) was then added to dissolve the mixture. Stirring was continued at room temperature overnight. After completion of the reaction, the mixture was concentrated to remove most of the methanol, and the residue was purified by C18 reverse-phase column chromatography (H2O / acetonitrile = 100:0 to 70:30) to obtain compound A111-1 (5.2 g, 64% yield). MS: 349.16 [M+H] + .

[1091] Step 2: Synthesis of compound A111-2

[1092] 8 mL of concentrated sulfuric acid was slowly added to 1 mL of water and the temperature was raised to 60°C. Compound A111-1 (2.6 g, 7.46 mmol) was added to the system in batches and reacted at 60°C for 4 hours. Then 20 mL of water was added and the temperature was raised to 100°C for 8 hours. LCMS monitored the complete reaction of the raw material. Cooled the temperature and crushed ice was added. Adjust the pH to 9-10 with NaOH, extract with DCM 4-5 times, combine the organic phases, wash with saturated brine, and dry over anhydrous sodium sulfate. Concentration gave the white solid product A111-2 (1.06 g, yield: 47.6%), MS: 299.17 [M+H] +

[1093] Step 3: Synthesis of compound A111-3

[1094] Compound A111-2 (1000 mg, 3.35 mmol) was added to THF (10 mL) and stirred to dissolve. Under nitrogen, a 2.5 M lithium aluminum hydride THF solution (5.5 mL) was added dropwise. After addition, the temperature was raised to 60°C and the reaction was allowed to proceed for 4 hours. LCMS was used to monitor the reaction until completion. The temperature was then lowered and the reaction was quenched by adding 0.5 mL of water and 1 mL of 15% aqueous NaOH. The reaction was filtered and the filtrate was concentrated to obtain crude A111-3, which was used directly in the next step. MS: 271.21 [M+H] +

[1095] Step 4: Synthesis of compound A111-4

[1096] Compound A111-3 (120 mg, 0.44 mmol) was added to methanol (4 mL), followed by 30% aqueous formaldehyde solution (2 mL), sodium cyanoborohydride (83.67 mg, 1.33 mmol), and 2 drops of acetic acid. After the addition was complete, the temperature was raised to 60°C and the reaction was allowed to proceed for 2 hours. LCMS was used to monitor the reaction until completion. The temperature was then lowered, and 10 mL of water and 20 mL of DCM were added, stirred, and the layers separated. The organic phase was dried and concentrated to afford crude A111-4, which was used directly in the next step. MS: 285.23 [M+H] +

[1097] Step 5: Synthesis of compound A111-5

[1098] The crude product of compound A111-4 (130 mg) was added to ethanol (5 mL), followed by the addition of Pd / C (10 mg). The hydrogen atmosphere was replaced three times. The temperature was raised to 50°C and the reaction was allowed to proceed for 4 hours. LCMS was used to monitor the reaction until it was complete, then the temperature was lowered and the mixture was filtered. The filtrate was concentrated to obtain the crude product of A111-5, which was used directly in the next step. MS: 195.18 [M+H] +

[1099] Step 6: Synthesis of Compound A111

[1100] Compound A02-8 (50 mg, 0.10 mmol) was added to dioxane (5 mL), followed by A111-5 (62.04 mg, 0.32 mmol), Pd2(dba)3 (29.3 mg, 0.03 mmol), Xphos (23.78 mg, 0.05 mmol), and sodium tert-butoxide (46.07 mg, 0.48 mmol). After the addition was complete, the atmosphere was purged with nitrogen three times. The temperature was raised to 100°C and the reaction was allowed to react for 2 h. LCMS was used to monitor the reaction until completion. The mixture was diluted with 20 mL of DCM and washed with water and then saturated brine. The organic phase was concentrated. The residue was purified by prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). The product A111 (8.5 mg, yield: 2.7%) was obtained, MS: 609.36 [M+H] +

[1101] The following final product was prepared in a similar manner to Example 111

[1102] Example 132 Synthesis of Compound A132

[1103] 2 5 ,2 6 -Difluoro-11 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzoic acid cycloundecane-3-one

[1104] Step 1: Synthesis of compound A132-1

[1105] Methyl 3-bromo-4,5-difluorobenzoate (1 g, 3.98 mmol), pinacol diboronate (2.53 g, 9.96 mmol), potassium acetate (1.17 g, 11.95 mmol), PdCl₂dppfCH₂Cl₂ (0.33 g, 0.4 mmol), and anhydrous 1,4-dioxane (20 mL) were added sequentially to a three-necked flask. The temperature was raised to 65°C under nitrogen and the reaction was allowed to proceed for 15 h. The reaction was monitored by TLC until nearly complete. The product was then concentrated and the residue was dissolved in dichloromethane (50 mL) and washed sequentially with tap water (100 mL) and saturated brine (100 mL). The organic layer was concentrated and purified by column chromatography (PE:EA = 5:1). The eluate was concentrated to obtain product A132-1.

[1106] Step 2: Synthesis of compound A132-2

[1107] Compound A132-1 (2.34 g, 7.85 mmol) was added to toluene (16 mL), followed by the addition of A40-3 (0.46 g, 1.31 mmol), tris(dibenzylideneacetone)dipalladium(0) (120 mg, 0.13 mmol), n-butyldi(1-adamantyl)phosphine (94 mg, 0.26 mmol), cesium carbonate (1.28 g, 3.93 mmol), and water (4 mL). The atmosphere in the reaction system was replaced with nitrogen three times, and the mixture was reacted at 65°C under a nitrogen balloon for 3 hours. LCMS monitored the reaction to be essentially complete, and the mixture was cooled to room temperature and concentrated. The residue was dissolved in dichloromethane (50 mL), washed sequentially with tap water (100 mL) and saturated brine (100 mL), and the organic layer was concentrated and separated and purified by column chromatography (PE:EA=1:1). The eluate was concentrated to obtain product A132-2.

[1108] Step 3: Synthesis of compound A132-3

[1109] Compound A132-2 (0.66 g, 1.66 mmol), LiOH-H2O (0.21 g, 4.97 mmol), methanol (15 mL), and water (3 mL) were mixed uniformly and allowed to react at room temperature for 15 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 4-5, and solids gradually precipitated. The solids were filtered, and the filter cake was washed with tap water. Toluene was added to the filter cake, and the mixture was concentrated under reduced pressure to obtain the product compound A132-3 (0.29 g, yield: 45%). MS: 385.32 [M+H] +

[1110] Step 4: Synthesis of compound A132-4

[1111] Compound A02-2 (10.00 g, 32.99 mmol) was added to MeOH (50 mL), followed by DCM (50 mL) and stirred to dissolve. A solution of ammonium chloride (8.82 g, 164.93 mmol) in water (100 mL) was then added. After stirring, zinc powder (10.79 g, 164.93 mmol) was added in portions and stirred at room temperature for 30 minutes. LCMS monitored the reaction completion, and 150 mL of DCM and 100 mL of water were added. The mixture was filtered, separated, and the organic phase was washed with saturated brine and concentrated to give product A132-4 (8.68 g, yield: 96.3%). MS: 273.10, 275.10 [M+H] +

[1112] Step 5: Synthesis of compound A132-5

[1113] Compound A132-4 (8.65 g, 31.67 mmol), ethanol (200 mL), and cyanogen bromide (4.02 g, 38.00 mmol) were mixed and allowed to react overnight at room temperature. LCMS monitored the reaction completion. 300 mL of water was added, and the pH was adjusted to 9-10 with a 10% aqueous potassium carbonate solution. Extraction was performed with 2 x 150 mL of ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was added with 150 mL of EA:PE (1:3), sonicated, and filtered to obtain compound A132-5 (8.21 g, yield: 86.9%). MS: 298.20, 300.20 [M+H] +

[1114] Step 6: Synthesis of Compound A132-6

[1115] Compound A132-5 (9.20 g, 30.85 mmol) and imidazole (4.20 g, 61.71 mmol) were added to DCM (200 mL). Tert-butyldimethylsilyl chloride (6.05 g, 40.11 mmol) was added portionwise and the mixture was stirred at room temperature. The reaction was monitored for completion by LCMS. The system was washed with water (100 mL), and the organic phase was concentrated under reduced pressure. The residue was subjected to reverse phase preparative separation (water-acetonitrile) to obtain product A132-6 (10.02 g, yield: 78.7%). MS: 412.20, 414.20 [M+H] +

[1116] Step 7: Synthesis of Compound A132-7

[1117] Compound A132-3 (0.29 g, 0.75 mmol), DIEA (0.62 mL, 3.77 mmol), and DCM (15 mL) were mixed uniformly, HATU (0.28 g, 0.74 mmol) was added under ice bath, and the mixture was stirred at this temperature for 5 min. A132-6 (0.26 g, 0.64 mmol) was added, and the mixture was stirred at this temperature for 1 h. The temperature was gradually raised to room temperature and stirred for 1 h. The reaction was monitored by LCMS. Saturated aqueous potassium carbonate solution was added to quench the reaction, and 3 x 20 mL of DCM were used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and spin-dried. The mixture was purified by PLC using DCM:MeOH = 20:1 as the developing solvent to obtain A132-7 (380 mg, yield: 64.7%).

[1118] Step 8: Synthesis of Compound A132-8

[1119] A132-7 (380 mg, 0.49 mmol) was dissolved in dichloromethane (3 mL), trifluoroacetic acid (20 mL) was added dropwise, and the mixture was stirred at room temperature for 15 hours to stop the reaction. The solvent was evaporated under reduced pressure, and the residue was dissolved in 5 mL of dichloromethane and methanol (5 mL). A saturated aqueous potassium carbonate solution (20 mL) was added and stirred at room temperature for 3 hours. The reaction was monitored by LCMS. The solvent was evaporated under reduced pressure, and dichloromethane (50 mL) and anhydrous methanol (5 mL) were added to dissolve the mixture. The mixture was sonicated and filtered. The filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated to give A132-8 (250 mg, yield: 95.8%). MS: 534.09, 536.09 [M+H] +

[1120] Step 9: Synthesis of Compound A132-9

[1121] A132-8 (250 mg, 0.47 mmol), CMBP (564 mg, 2.34 mmol), and toluene (15 mL) were added sequentially to a single-necked flask, and the temperature was raised to 115°C for reaction for 5 h. TLC showed the formation of new spots. The reaction was stopped and the solvent was evaporated under reduced pressure. The residue was purified by PLC (DCM:MeOH=15:1) to give A132-9 (50 mg, yield: 20.7%), MS: 516.08, 518.08 [M+H] +

[1122] Step 10: Synthesis of compound A132

[1123] Compound A132-9 (22 mg, 0.04 mmol), compound 3-methyl-3,9-diazaspiro[5,5]undecane (14 mg, 0.09 mmol), Pd 2( dba)3 (6 mg, 0.01 mmol), Xphos (6 mg, 0.01 mmol), sodium tert-butoxide (8 mg, 0.09 mmol), and dioxane (2 mL) were mixed uniformly and reacted at 100°C for 2 h under nitrogen. LCMS monitored the reaction completion and the product was purified by PLC (DCM:MeOH = 10:1) to obtain the product compound A132 (3 mg, yield: 11.6%). MS: 604.31 [M+H] +

[1124] Example 160 Synthesis of Compound A160

[1125] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 5 -Nitrile

[1126] Step 1: Synthesis of compound A160-1

[1127] In a 100 mL single-necked bottle, methyl 3-bromo-5-cyanobenzoate (900 mg, 3.75 mmol), bis-pinacol borate (1.14 g, 4.5 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (0.36 g, 0.37 mmol), potassium acetate (735 mg, 7.5 mmol) and 1,4-dioxane (10 mL) were mixed evenly, protected by nitrogen, and reacted at 80 ° C for 12 h. The reaction mixture was cooled to room temperature, and 4-iodo-2-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1,2-dihydro-3H-pyrazol-3-one (1.11 g, 3.13 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (0.36 g, 0.37 mmol), potassium carbonate (1.30 g, 9.4 mmol), and pure water (2 mL) were added under nitrogen protection. The reaction was continued at 80°C for 6 h. The reaction mixture was cooled to room temperature, 50 mL of ethyl acetate was added, and the mixture was washed with saturated brine 3 x 20 mL. The organic phase was dried and purified by column chromatography using a PE / EA ratio of 3 / 1 to obtain compound A160-1 (400 mg, 1.03 mmol, 33% yield). MS: 388.16 [M+H] +

[1128] Step 2: Synthesis of compound A160-2

[1129] In a reaction flask, A160-1 (400 mg, 1.03 mmol), lithium hydroxide (75 mg, 13.10 mmol), THF (3 mL), methanol (3 mL), and purified water (3 mL) were mixed uniformly and stirred at room temperature for 4 h. The organic solvent was concentrated, purified water (10 mL) was added, and the pH was adjusted to 5 with dilute hydrochloric acid. The mixture was filtered, and the filter cake was rinsed with water 3 x 15 mL. The filter cake was dried under vacuum to obtain the product compound A160-2 (320 mg, yield: 83%). MS: 374.15 [M+H] +

[1130] Step 3: Synthesis of compound A160-3

[1131] A160-2 (450 mg, 1.20 mmol), A132-6 (497 mg, 1.20 mmol), DIEA (312 mg, 2.41 mmol), and DCM (5 mL) were added to a reaction flask. HATU (413 mg, 1.08 mmol) was added under ice-cooling. The reaction was allowed to react at room temperature for 2 h. LCMS monitored the reaction completion. 50 mL of DCM was added, and the mixture was washed with 20 mL of saturated brine. The organic phase was dried and slurried with ethyl acetate (5 mL). The mixture was filtered to obtain the product compound A160-3 (700 mg, yield: 76%). MS: 767.27, 769.27 [M+H] +

[1132] Step 4: Synthesis of compound A160-4

[1133] A160-3 (600 mg, 0.78 mmol), THF (10 mL), and a 1M / mL solution of TBAF in THF were added to a reaction flask and reacted at 70°C for 12 h. LCMS monitoring indicated that the reaction was essentially complete. The product was then concentrated and added dropwise to 30 mL of pure water. The filter cake was filtered and rinsed with 3 x 15 mL of water. The filter cake was then dried under vacuum to afford compound A160-4 (600 mg, 81% yield). MS: 523.10, 525.10 [M+H] +

[1134] Step 5: Synthesis of compound A160-5

[1135] Compound A160-4 (0.30 g, 0.57 mmol), CMBP (0.69 g, 2.87 mmol), and toluene (3 mL) were mixed and reacted at 130°C for 2 h. The reaction was complete after LCMS monitoring. The mixture was cooled to room temperature and filtered. The filter cake was rinsed with 3 x 3 mL of toluene and dried under vacuum to obtain compound A160-5 (205 mg, yield: 71%). MS: 505.09, 507.09 [M+H] +

[1136] Step 6: Synthesis of Compound A160

[1137] Compound A160-5 (80 mg, 0.16 mmol), 3-methyl-3,9-diazaspiro[5.5]undecane (80 mg, 0.47 mmol), Pd 2(dba)3 (15 mg, 0.02 mmol), Xphos (15 mg, 0.03 mmol), sodium tert-butoxide (46 mg, 0.47 mmol), and dioxane (2 mL) were mixed uniformly and reacted at 100°C for 12 h under nitrogen atmosphere. LCMS monitored the reaction, confirming the near-complete reaction. The product was then prepared by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). The product A160 (14 mg, 14.9% yield) was obtained. MS: 593.33 [M+H] +

[1138] The following final products were prepared in a similar manner to Example 132 and Example 160:

[1139] Example 136 Synthesis of Compound A136

[1140] 5 5 -Fluorine-1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-2-one

[1141] Step 1: Synthesis of compound A136-1

[1142] In a 250 mL single-necked flask, 1-bromo-2,5-difluoro-4-nitrobenzene (10 g, 42.0 mmol) was dissolved in DMF (50 mL). Potassium carbonate (11.62 g, 84.0 mmol) and 5-aminopentan-1-ol (4.77 g, 46.22 mmol) were added and allowed to react overnight at room temperature. After the disappearance of the starting material as monitored by TLC, the reaction solution was poured into 400 mL of water. A large amount of orange-red solid precipitated. The solid was filtered and rinsed with 100 mL of water twice. The filter cake was dried under vacuum to obtain 13.0 g of product A136-1 (yield: 96%). MS: 321.24, 323.23 [M+H] +

[1143] Step 2: Synthesis of compound A136-2

[1144] In a 100 mL single-necked bottle, A136-1 (2.00 g, 6.23 mmol) was dissolved in DCM (30 mL). Triethylamine (2.6 mL, 18.68 mmol), p-toluenesulfonyl chloride (1.42 g, 7.47 mmol), and DMAP (0.08 g, 0.62 mmol) were added. The mixture was allowed to react at room temperature for 4 hours. LCMS monitored the reaction for completion. 30 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was dried by spin drying and then purified by column chromatography using a PE / EA ratio of 2 / 1 to afford the product A136-2 (2.6 g, 88% yield). MS: 475.03, 477.03 [M+H] + .

[1145] Step 3: Synthesis of compound A136-3

[1146] In a 100 mL single-necked bottle, A02-1 (1.0 g, 4.04 mmol) was dissolved in DMF (20 mL). A136-2 (1.20 g, 3.96 mmol) and potassium carbonate (1.68 g, 12.13 mmol) were added. The temperature was raised to 70°C for 6 h. The reaction was complete as monitored by LCMS. 100 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic phase was dried by spin-drying and then purified by column chromatography (PE / EA = 1 / 1) to obtain the product A136-3 (1.88 g, yield: 84%). MS: 550.10, 552.10 [M+H] +

[1147] Step 4: Synthesis of compound A136-4

[1148] Compound A136-3 (1.88 g, 3.42 mmol) was dissolved in a mixture of methanol and dichloromethane (1:1, 20 mL:20 mL). Zinc powder (2.23 g, 34.2 mmol) was added, and a saturated aqueous solution of ammonium chloride (1.83 g, 34.2 mmol) was added dropwise. The reaction was allowed to react at room temperature. LCMS monitored the reaction for completion. The mixture was filtered, the organic solvent was removed by rotary evaporation, and then extracted with ethyl acetate (100 mL x 2). The organic phase was dried by rotary evaporation and purified by column chromatography (DCM / MeOH = 20 / 1) to give product A136-4 (1.3 g, yield: 73%). MS: 520.13, 522.13 [M+H] +

[1149] Step 5: Synthesis of compound A136-5

[1150] Compound A136-4 (1.24 g, 2.38 mmol) was dissolved in ethanol (50 mL), and cyanogen bromide (270 mg, 2.5 mmol) was added. The mixture was allowed to react at room temperature until no starting material was detected by LCMS. Saturated aqueous sodium bicarbonate solution was added to adjust the pH to 8. The organic solvent was removed by concentration under reduced pressure, and the mixture was extracted with DCM (100 mL x 2). The organic phase was dried by spin drying and then purified by column chromatography (DCM / MeOH = 20 / 1) to give product A136-5 (900 mg, yield: 70%). MS: 545.12, 547.12 [M+H] +

[1151] Step 6: Synthesis of Compound A136-6

[1152] Compound A136-5 (330 mg, 0.61 mmol) was dissolved in methanol (10 mL), and water (5 mL) and NaOH (50 mg, 1.21 mmol) were added. The mixture was mixed and allowed to react at room temperature for 3 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 7, and the mixture was extracted with ethyl acetate (100 mL x 2). The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give product A136-6 (210 mg, yield: 65%). MS: 531.11, 533.11 [M+H] +

[1153] Step 7: Synthesis of Compound A136-7

[1154] Compound A136-6 (200 mg, 0.38 mmol) and DIEA (0.19 mL, 1.13 mmol) were dissolved in dichloromethane (20 mL). HATU (140 mg, 0.38 mmol) was added at room temperature. After reacting for 1 hour, the temperature was raised to 70°C and the reaction was continued for 6 hours. LCMS monitored the reaction to be complete. The reaction was quenched by adding 20 mL of water, extracted with DCM (20 mL x 2), dried over anhydrous sodium sulfate, filtered, and the organic phase was spin-dried and column chromatography was performed using DCM / MeOH = 20 / 1 to obtain product A136-7 (160 mg, yield: 83%). MS: 513.10, 515.10 [M+H] +

[1155] Step 8: Synthesis of Compound A136

[1156] Compound A136-7 (100 mg, 0.19 mmol), 3-methyl-3,9-diazaspiro[5,5]undecane (70 mg, 0.39 mmol), sodium tert-butoxide (60 mg, 0.58 mmol), Xphos / 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (30 mg, 0.06 mmol) and Pd2(dba)3 / tris(dibenzylideneacetone)dipalladium (40 mg, 0.04 mmol) were added to 1,4-dioxane (10.00 mL) under nitrogen protection and reacted at 130°C for 2 hours. The reaction was monitored by LCMS to be complete. The reaction solution was filtered and dried, and directly prepared by Prep-HPLC using a luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile was adjusted from 17% to 50% in 20 mins). The product A136 (7.6 mg, yield: 6.3%) was obtained. MS: 601.33 [M+H] +

[1157] Example 137 Synthesis of Compound A137

[1158] 5 7 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1159] Step 1: Synthesis of compound A137-1

[1160] The synthesis method of compound A137-1 is the same as that of compound A02-4, except that compound A02-3 is replaced by compound 5-(tert-butyloxycarbonylamino) bromopentane. MS of compound A137-1: 433.24 [M+H] +

[1161] Step 2: Synthesis of compound A137-2

[1162] The synthesis method of compound A137-2 is the same as that of compound A03-10, except that compound A03-09 is replaced by compound A137-1. MS of compound A137-2: 333.18 [M+H] +

[1163] Step 3: Synthesis of compound A137-3

[1164] The synthesis method of compound A137-3 is the same as that of compound A02-2, except that 5-aminopentane-1-ol and 4-bromo-2-fluoro-1-nitrobenzene are replaced by compound A137-2 and 2,3-difluoro-4-bromonitrobenzene, respectively. MS of compound A137-3: 550.10, 552.10 [M+H] +

[1165] Step 4: Synthesis of compound A137-4

[1166] The synthesis method of compound A137-4 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A137-3. MS of compound A137-4: 520.13, 522.13 [M+H] +

[1167] Step 5: Synthesis of compound A137-5

[1168] The synthesis method of compound A137-5 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A137-4. MS of compound A137-5: 545.12, 547.12 [M+H] +

[1169] Step 6: Synthesis of Compound A137-6

[1170] The synthesis method of compound A137-6 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A137-5. MS of compound A137-6: 531.11, 533.11 [M+H] +

[1171] Step 7: Synthesis of Compound A137-7

[1172] The synthesis method of compound A137-7 is the same as that of compound A02-8, except that compound A02-7 is replaced by compound A137-6. MS of compound A137-7: 513.10, 515.10 [M+H] +

[1173] Step 8: Synthesis of Compound A137

[1174] The synthesis method of compound A137 is the same as that of compound A02, except that compound A02-8 and 2-methyl-2,7-diazaspiro[3.5]nonane are replaced by compound A137-7 and 3-methyl-3,9-diazaspiro[5,5]undecane, respectively. MS of compound A137: 601.33 [M+H] +

[1175] Example 138 Synthesis of Compound A138

[1176] 1 1 , 2 6 , 5 5 -Trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1177] Step 1: Synthesis of compound A138-1

[1178] The synthesis method of compound A138-1 is the same as that of compound A02-2, except that 5-aminopentane-1-ol and 4-bromo-2-fluoro-1-nitrobenzene are replaced by compound A137-2 and 2-bromo-4-fluoro-5-nitrotoluene, respectively. MS of compound A138-1: 546.13, 548.13 [M+H] +

[1179] Step 2: Synthesis of compound A138-2

[1180] The synthesis method of compound A138-2 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A138-1. MS of compound A138-2: 520.13, 522.13 [M+H] +

[1181] Step 3: Synthesis of compound A138-3

[1182] The synthesis method of compound A138-3 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A138-2. MS of compound A138-3: 541.15, 543.15 [M+H] +

[1183] Step 4: Synthesis of compound A138-4

[1184] The synthesis method of compound A138-4 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A138-3. MS of compound A138-4: 531.11, 533.11 [M+H] +

[1185] Step 5: Synthesis of compound A138-5

[1186] The synthesis method of compound A138-5 is the same as that of compound A02-8, except that compound A02-7 is replaced by compound A138-4. MS of compound A138-5: 509.12, 511.12 [M+H] +

[1187] Step 6: Synthesis of Compound A138

[1188] The synthesis method of compound A138 is the same as that of compound A02, except that compound A02-8 and 2-methyl-2,7-diazaspiro[3.5]nonane are replaced by compound A138-5 and 3-methyl-3,9-diazaspiro[5,5]undecane, respectively. MS of compound A138: 597.36 [M+H] +

[1189] Example 174 Synthesis of Compound A174

[1190] 5 5 -Methoxy-1 1 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-2-one

[1191] Step 1: Synthesis of compound A174-1

[1192] In a 250 mL single-necked flask, 2-bromo-4-fluoro-5-nitrophenol (11.7 g, 50 mmol) was dissolved in acetone (50 mL). Potassium carbonate (13.79 g, 100 mmol) and iodomethane (10.65 g, 75 mmol) were added, and the mixture was refluxed for 3 h. After the disappearance of the starting material as monitored by TLC, the reaction solution was poured into 400 mL of water. A large amount of solid precipitated, which was filtered and rinsed with 100 mL of water twice. The filter cake was dried in vacuo to obtain product A174-1 (11.8 g, yield: 95%).

[1193] Step 2: Synthesis of compound A174-2

[1194] In a 250 mL single-necked flask, A174-1 (10.0 g, 40.3 mmol) was dissolved in DMF (50 mL). Potassium carbonate (11.12 g, 80.6 mmol) and 5-aminopentan-1-ol (4.57 g, 44.33 mmol) were added and allowed to react overnight at room temperature. After the disappearance of the starting material by TLC monitoring, the reaction solution was poured into 400 mL of water. A large amount of orange-red solid precipitated. The solid was filtered, rinsed with 50 mL of water twice, and the filter cake was dried under vacuum to obtain product A174-2 (11.37 g, yield: 85%). MS: 333.04, 335.04 [M+H] + .

[1195] Step 3: Synthesis of compound A174-3

[1196] In a 250 mL single-necked bottle, A174-2 (9.96 g, 30.0 mmol) was dissolved in DCM (100 mL). Triethylamine (8.32 mL, 60.0 mmol), p-toluenesulfonyl chloride (6.84 g, 36.0 mmol), and DMAP (366 mg, 3 mmol) were added and allowed to react at room temperature for 6 hours. The reaction was monitored for completion by LCMS. 100 mL of water was added to the reaction solution, and the mixture was extracted with DCM (100 mL x 2). The organic phase was dried by spin drying and purified by column chromatography using a PE / EA ratio of 1 / 1 to afford the product A174-3 (12.83 g, 88% yield). MS: 487.05, 489.05 [M+H] + .

[1197] Step 4: Synthesis of compound A174-4

[1198] In a 250 mL single-necked bottle, A02-1 (2.0 g, 8.08 mmol) was dissolved in DMF (50 mL). A174-3 (4.12 g, 8.48 mmol) and potassium carbonate (2.23 g, 16.16 mmol) were added. The temperature was raised to 70°C and the reaction mixture was allowed to react for 6 h. The reaction was monitored by LCMS for completion. 100 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic phase was dried by spin-drying and then purified by column chromatography (PE / EA = 1 / 1) to obtain the product A174-4 (3.72 g, yield: 82%). MS: 562.12, 556.12 [M+H] +

[1199] Step 5: Synthesis of compound A174-5

[1200] Compound A174-4 (3.72 g, 6.63 mmol) was dissolved in a mixture of methanol and dichloromethane (1:1, 50 mL:50 mL). Zinc powder (4.24 g, 66.3 mmol) was added, and a saturated aqueous solution of ammonium chloride (3.51 g, 66.3 mmol) was added dropwise. The mixture was allowed to react at room temperature for 2 hours. The reaction was monitored by LCMS for completion. The mixture was filtered, the organic solvent was removed by rotary evaporation, and then extracted with ethyl acetate (100 mL x 2). The organic phase was dried by rotary evaporation and purified by column chromatography (DCM / MeOH = 20 / 1) to give product A174-5 (2.75 g, yield: 78%). MS: 532.15, 534.15 [M+H] +

[1201] Step 6: Synthesis of Compound A174-6

[1202] Compound A174-5 (2.75 g, 5.2 mmol) was dissolved in a mixed solvent of acetonitrile (30 mL) and water (10 mL). Cyanogen bromide (549 mg, 5.2 mmol) was added and the mixture was allowed to react at room temperature under nitrogen for 2 hours. LCMS confirmed the absence of starting material. Saturated aqueous sodium bicarbonate solution was added to adjust the pH to 8. The organic solvent was removed by concentration under reduced pressure and the mixture was extracted with DCM (100 mL x 2). The organic phase was dried by spin drying and then purified by column chromatography (DCM / MeOH = 20 / 1) to give product A174-6 (432 mg, yield: 15%). MS: 557.14, 559.14 [M+H] +

[1203] Step 7: Synthesis of Compound A174-7

[1204] Compound A174-6 (432 mg, 0.77 mmol) was dissolved in methanol (10 mL), and water (5 mL) and NaOH (124 mg, 3.11 mmol) were added. The mixture was mixed and allowed to react at room temperature for 3 h. The reaction was monitored by LCMS. The pH was adjusted to 7, and the mixture was extracted with ethyl acetate (100 mL x 2). The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give product A174-7 (315 mg, yield: 75%). MS: 543.13, 545.13 [M+H] +

[1205] Step 8: Synthesis of Compound A174-8

[1206] Compound A174-7 (315 mg, 0.58 mmol) and DIEA (0.29 mL, 1.74 mmol) were dissolved in dichloromethane (20 mL). HATU (264 mg, 0.70 mmol) was added at room temperature. After one hour of reaction, the temperature was raised to 70°C and the reaction was continued for another 6 hours. LCMS monitored the reaction to be complete. The reaction was quenched by adding 20 mL of water and extracted with DCM (20 mL x 2). The mixture was dried over anhydrous sodium sulfate and filtered. The organic phase was then evaporated to dryness and purified by column chromatography using DCM / MeOH = 20 / 1 to afford product A174-8 (247 mg, yield: 81%). MS: 525.12, 527.12 [M+H] +

[1207] Step 9: Synthesis of compound A174

[1208] Compound A174-8 (105 mg, 0.20 mmol), 3-(oxetane-3-yl)-3,9-diazaspiro[5.5]undecane (84 mg, 0.4 mmol), sodium tert-butoxide (60 mg, 0.6 mmol), Xphos / 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (58 mg, 0.06 mmol) and Pd2(dba)3 / tris(dibenzylideneacetone)dipalladium (40 mg, 0.04 mmol) were added to 1,4-dioxane (10.00 mL) under nitrogen protection and reacted at 130°C for 2 hours. The reaction was monitored by LCMS to be complete. The reaction solution was filtered and dried, and directly prepared by Prep-HPLC using a luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid aqueous solution, B: acetonitrile; acetonitrile was adjusted from 17% to 50% in 20 mins). The product A174 (9.1 mg, yield: 7.1%) was obtained. MS: 655.36 [M+H] +

[1209] Example 184 Synthesis of Compound A184

[1210] 5 5 -Chloro-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one

[1211] Step 1: Synthesis of compound A184-1

[1212] In a reaction flask, 1-bromo-2-chloro-5-fluoro-4-nitrobenzene (1.02 g, 4.01 mmol), 5-aminopentan-1-ol (0.50 g, 4.85 mmol), potassium carbonate (1.11 g, 8.03 mmol), and DMF (10 mL) were mixed thoroughly and stirred at room temperature overnight. The reaction mixture was poured into 50 mL of water and extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was added to 50 mL of petroleum ether:ethyl acetate (10:1), slurried, and filtered to obtain product A184-1 (1.22 g, yield: 90%). MS: 336.99, 338.99 [M+H] +

[1213] Step 2: Synthesis of compound A184-2

[1214] A184-1 (1.22 g, 3.61 mmol) and triethylamine (0.73 g, 7.21 mol) were added to a reaction flask in DCM (20 mL). p-Toluenesulfonyl chloride (0.83 g, 4.35 mmol) was added and the mixture was allowed to react at room temperature for 3 h. The reaction was monitored by LCMS for completion. The mixture was then dried and purified by column chromatography using PE / EA = 1 / 1 to obtain the product compound A184-2 (1.34 g, yield: 75.6%). MS: 491.00, 493.00 [M+H] +

[1215] Step 3: Synthesis of compound A184-3

[1216] In a 100 mL single-necked bottle, compound A184-2 (1.30 g, 2.64 mmol), A02-1 (0.66 g, 2.67 mmol), potassium carbonate (0.78 g, 5.64 mmol), and DMF (15 mL) were mixed and reacted at 60°C for 6 h. The reaction was monitored by LCMS until complete. 50 mL of ethyl acetate was added, and the mixture was washed with 2 x 40 mL of saturated brine. The organic phase was dried and purified by column chromatography using DCM / EA = 3 / 1 to afford compound A184-3 (1.12 g, 75% yield). MS: 566.07, 568.07 [M+H] +

[1217] Step 4: Synthesis of compound A184-4

[1218] Compound A184-3 (1.09 g, 1.92 mmol) was added to MeOH (5 mL), followed by DCM (5 mL) and stirred to dissolve. Saturated aqueous ammonium chloride (10 mL) was then added. After stirring, Zn powder (1.02 g, 15.95 mmol) was added portionwise and stirred at room temperature for 1 hour. LCMS monitored the reaction completion, and 20 mL of DCM and 20 mL of water were added. The layers were separated, and the organic phase was washed with saturated brine and concentrated to afford product A184-4 (0.98 g, 95% yield). MS: 536.10, 538.10 [M+H] +

[1219] Step 5: Synthesis of compound A184-5

[1220] Compound A184-4 (0.98 g, 1.83 mmol), cyanogen bromide (225.0 mg, 2.12 mmol), methanol (10 mL), and water (2 mL) were mixed and allowed to react overnight at room temperature. The reaction was complete after LCMS monitoring. 30 mL of water was added, and the pH was adjusted to 8-9 with 10% aqueous potassium carbonate solution. The mixture was extracted with 3 x 20 mL of DCM and concentrated under reduced pressure to obtain compound A184-5 (0.97 g, yield: 94.0%). MS: 561.09, 563.09 [M+H] +

[1221] Step 6: Synthesis of Compound A184-6

[1222] Compound A184-5 (0.91 g, 1.62 mmol), lithium hydroxide monohydrate (0.45 g, 10.72 mmol), methanol (5 mL), water (5 mL), and tetrahydrofuran (5 mL) were mixed and reacted at room temperature for 3 h. The reaction was complete after LCMS monitoring. The pH was adjusted to 6-7, and the mixture was extracted with 3 x 30 mL of DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain compound A184-6 (0.69 g, yield: 79.6%). MS: 547.08, 549.08 [M+H] +

[1223] Step 7: Synthesis of Compound A184-7

[1224] Compound A184-6 (0.64 g, 1.17 mmol), DIEA (530.0 mg, 4.10 mmol), and DMF (8 mL) were mixed uniformly and HATU (0.49 g, 1.29 mmol) was added under ice-cooling. The mixture was allowed to react at room temperature for 2 h. The reaction was monitored by LCMS until complete. The reaction was quenched by adding 30 mL of water and extracted with 3 x 20 mL of DCM. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and dried by spin chromatography using a DCM / MeOH (20 / 1) column to afford A184-7 (0.34 g, 54.7% yield). MS: 529.07, 531.07 [M+H] +

[1225] Step 8: Synthesis of Compound A184

[1226] Compound A184-7 (120.6 mg, 0.23 mmol), dioxane (5 mL), 3-(oxetane-3-yl)-3,9-diazaspiro[5.5]undecane (240.6 mg, 1.14 mmol), Pd2(dba)3 (21.2 mg, 0.023 mmol), Xphos (25.3 mg, 0.053 mmol), and sodium tert-butoxide (66.3 mg, 0.69 mmol) were mixed uniformly and reacted at 100°C for 3 h under nitrogen atmosphere. The mixture was concentrated under reduced pressure, and the residue was separated by Prep-HPLC using a Luna C18 column, 30*250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile was adjusted from 17% to 50% over 20 mins). Compound A184 (18.3 mg, 12.1% yield) was obtained. MS: 659.31 [M+H] +

[1227] Example 192 Synthesis of Compound A192

[1228] 1 1 , 26 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 5 -Nitrile

[1229] Step 1: Synthesis of compound A192-1

[1230] In a reaction flask, 2-bromo-4-fluoro-5-nitrobenzonitrile (2.00 g, 8.16 mmol), 5-aminopentan-1-ol (0.93 g, 8.97 mmol), potassium carbonate (3.38 g, 24.49 mmol), and DMF (20 mL) were mixed thoroughly and stirred at room temperature overnight. The reaction mixture was poured into 100 mL of ice water, filtered, rinsed with 3 x 15 mL of water, and the filter cake was dried under vacuum to obtain the product, compound A192-1 (2.50 g, yield: 93%). MS: 328.02, 330.02 [M+H] +

[1231] Step 2: Synthesis of compound A192-2

[1232] A192-1 (2.50 g, 7.62 mmol), triethylamine (2.11 mL, 15.24 mmol), and DCM (30 mL) were added to a reaction flask. MsCl (1.05 g, 9.14 mmol) was added under ice-cooling. The reaction was allowed to react at room temperature for 2 h. The reaction was monitored for completion by LCMS. The product was then dried and purified by column chromatography using PE / EA = 1 / 1 to obtain the product compound A192-2 (2.85 g, yield: 92%). MS: 406.00, 408.00 [M+H] +

[1233] Step 3: Synthesis of compound A192-3

[1234] In a 100 mL single-necked bottle, compound A192-2 (1.00 g, 2.46 mmol), A02-1 (0.61 g, 2.46 mmol), potassium carbonate (0.68 g, 4.92 mmol), and DMF (10 mL) were mixed and reacted at 60°C for 6 h. The reaction was monitored by LCMS until complete. 40 mL of ethyl acetate was added, and the mixture was washed with 3 x 30 mL of saturated brine. The organic phase was dried and purified by column chromatography using DCM / EA = 3 / 1 to obtain compound A192-3 (1.26 g, 92% yield). MS: 557.11, 559.11 [M+H] +

[1235] Step 4: Synthesis of compound A192-4

[1236] Compound A192-3 (1.26 g, 2.26 mmol), iron powder (0.63 g, 11.30 mmol), ammonium chloride (0.60 g, 11.30 mmol), ethanol (12 mL), and H2O (6 mL) were mixed and reacted at 60°C for 1 h. The reaction was complete after LCMS monitoring. The mixture was filtered, cooled, and dried by spin chromatography. The product, compound A192-4 (1.07 g, yield: 90%), was obtained by column chromatography using DCM / MeOH = 10 / 1. MS: 527.13, 529.13 [M+H] +

[1237] Step 5: Synthesis of compound A192-5

[1238] Compound A192-4 (1.07 g, 2.03 mmol), cyanogen bromide (236 mg, 2.23 mmol), methanol (10 mL), and water (2 mL) were mixed and reacted at 70°C for 1 h. The reaction was complete after LCMS monitoring. The pH was adjusted to 8, and the mixture was extracted with 3 x 50 mL of DCM. The mixture was then dried to give compound A192-5 (1.06 g, yield: 95%). MS: 552.13, 554.13 [M+H] +

[1239] Step 6: Synthesis of Compound A192-6

[1240] Compound A192-5 (1.06 g, 1.93 mmol), NaOH (385 mg, 9.64 mmol), methanol (10 mL), and water (10 mL) were mixed and reacted at room temperature for 1 h. The reaction was monitored by LCMS for completion. The pH was adjusted to 7, and the mixture was extracted with 3 x 50 mL DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give compound A192-6 (930 mg, yield: 90%). MS: 538.11, 540.11 [M+H] +

[1241] Step 7: Synthesis of Compound A192-7

[1242] Compound A192-6 (0.93 g, 1.73 mmol), DIEA (0.57 mL, 3.45 mmol), and DCM (10 mL) were mixed uniformly. HATU (0.65 g, 1.73 mmol) was added under ice-cooling. The mixture was allowed to react at 10°C for 30 min. The reaction was monitored by LCMS. 100 mL of water was added to quench the reaction, and the mixture was extracted with 3 x 50 mL of DCM. The mixture was dried over anhydrous sodium sulfate, filtered, and slurried in 50 mL of DCM to obtain compound A192-7 (0.36 g, 40% yield). MS: 520.10, 522.10 [M+H] +

[1243] Step 8: Synthesis of Compound A192

[1244] Compound A192-7 (100 mg, 0.19 mmol), 3-(oxetane-3-yl)-3,9-diazaspiro[5.5]undecane (61 mg, 0.28 mmol), Pd2(dba)3 (52 mg, 0.057 mmol), Xphos (18 mg, 0.038 mmol), sodium tert-butoxide (74 mg, 0.76 mmol), and dioxane (5 mL) were mixed and reacted at 100°C for 8 h under nitrogen atmosphere. The reaction was monitored for completion by LCMS. Flash reverse phase preparative chromatography (mobile phase A: 0.05% FA, water; mobile phase B: ACN; gradient 0-75% B over 20 min) afforded the product, compound A192 (20 mg, 0.03 mmol, 16.1% yield). MS: 650.35 [M+H] +

[1245] The following final products were prepared in a similar manner to Examples 136-138, Example 174, Example 184, and Example 192.

[1246] Example 162 Synthesis of Compound A162

[1247] 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(7,5)-benzofurancycloundecan-3-one

[1248] Step 1: Synthesis of compound A162-1

[1249] In a 50 mL single-necked bottle, methyl 7-bromo-1-benzofuran-5-carboxylate (500 mg, 1.96 mmol), pinacol diboron (747 mg, 2.94 mmol), potassium acetate (385 mg, 3.92 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (160 mg, 0.2 mmol) were dispersed in 1,4-dioxane (10 mL) under nitrogen. Heat to 80°C in an oil bath for 3 hours. TLC confirmed the reaction was complete. Cool to room temperature. Add 50 mL of water and extract with 50 mL of ethyl acetate. Dry the organic phase over anhydrous sodium sulfate, filter, and concentrate. Purify by column chromatography (PE / EA = 8 / 1) to obtain product A162-1 (580 mg, 98% yield).

[1250] Step 2: Synthesis of compound A162-2

[1251] In a 100 mL single-necked bottle, A162-1 (580 mg, 1.92 mmol), A40-3 (816 mg, 2.30 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (157 mg, 0.19 mmol), and potassium carbonate were dispersed in 1,4-dioxane (20 mL) and water (3 mL) under nitrogen protection. The mixture was heated to 80°C in an oil bath for 8 hours. TLC monitoring indicated that the reaction was complete. 30 mL of water was added and the mixture was extracted with 50 mL of ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification was performed by column chromatography (PE / EA = 3 / 1). The product A162-2 (700 mg, yield: 90.59%) was obtained. MS: 403.16 [M+H] +

[1252] Step 3: Synthesis of compound A162-3

[1253] In a 50 mL single-necked flask, A162-2 (700 mg, 1.74 mmol) was dissolved in methanol (10 mL). Sodium hydroxide (140 mg, 3.48 mmol) and water (2 mL) were added. The reaction was allowed to react at room temperature for 12 hours. TLC monitoring indicated that the reaction was complete. 5 mL of water was added and the mixture was concentrated under reduced pressure to remove the methanol. The pH was adjusted to 3 with 2 mol / L dilute hydrochloric acid. A large amount of solid precipitated. The mixture was filtered and the filter cake was dried to obtain the product A162-3 (490 mg, yield: 72.53%). MS: 389.15 [M+H] +

[1254] Step 4: Synthesis of compound A162-4

[1255] In a 50 mL single-necked bottle, A162-3 (250 mg, 0.64 mmol), A132-6 (265 mg, 0.64 mmol), and HATU (245 mg, 0.64 mmol) were dissolved in DCM (10 mL). Stir and cool. DIEA (208 mg, 1.61 mmol) was added at 0°C. After the addition was complete, the mixture was naturally warmed to room temperature and reacted for 12 hours. LCMS monitoring was performed. After the reaction was complete, 50 mL of DCM was added and the mixture was washed with 30 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification was performed by column chromatography (PE / EA = 1 / 1). The product A162-4 (470 mg, yield: 93.29%) was obtained. MS: 782.27 [M+H] +

[1256] Step 5: Synthesis of compound A162-5

[1257] In a 50 mL single-necked bottle, A162-4 (520 mg, 0.66 mmol) was dissolved in THF (10 mL) and TBAF (1 mol / L) (3.5 mL, 13.28 mmol) was added. The mixture was heated to 70°C in an oil bath and reacted for 12 hours. LCMS monitoring confirmed the reaction was complete. The system was directly concentrated. The concentrate was slurried in 30 mL of water. The mixture was filtered and the filter cake was dried. The product A162-5 (360 mg, yield: 100%) was obtained. MS: 538.10 [M+H] +

[1258] Step 6: Synthesis of Compound A162-6

[1259] In a 10 mL sealed tube, A162-5 (260 mg, 0.48 mmol) was dissolved in toluene (2 mL) and CMBP (350 mg, 1.45 mmol) was added. The mixture was heated to 130°C in an oil bath for 1 hour. LCMS confirmed the reaction was complete. The temperature was cooled to room temperature. The system was concentrated, the concentrate was slurried with a mixed solvent (PE / EA = 1 / 1), filtered, and the filter cake was dried. The product A162-6 (130 mg, yield: 51.73%) was obtained. MS: 520.09 [M+H] +

[1260] Step 6: Synthesis of Compound A162

[1261] A162-6 (50 mg, 0.1 mmol), 3-methyl-3,9-diazaspiro[5,5]undecane (81 mg, 0.48 mmol), Pd2(dba)3 (18 mg, 0.02 mmol), Xphos (10 mg, 0.02 mmol), and potassium tert-butoxide (22 mg, 0.19 mmol) were dispersed in 1,4-dioxane (2 mL). The mixture was heated to 100°C in an oil bath under nitrogen for 3 hours. LCMS monitoring confirmed the completion of the reaction. The system was directly concentrated and purified by Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile was adjusted from 17% to 50% over 20 min). The product A162 (33 mg, yield: 55.37%) was obtained. MS: 608.33 [M+H] +

[1262] The following final product was prepared in a similar manner to Example 162

[1263] Example 205 Synthesis of Compound A205

[1264] 1 4 ,1 5 -Difluoro-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undecen-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(1,2)-benzocycloundecane-3-one

[1265] Step 1: Synthesis of compound A205-1

[1266] In a 100 mL single-necked bottle, (4,5-difluoro-2-hydroxyphenyl)boronic acid (500 mg, 2.88 mmol), 5-hydroxy-1-methylpyrazole (640 mg, 3.45 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (234 mg, 0.29 mmol), cesium carbonate (1.87 g, 5.75 mmol), and 1,4-dioxane (20 mL) were mixed with water (4 mL). The mixture was reacted at 100°C under nitrogen for 6 h. The disappearance of the starting material was monitored by TLC. The reaction mixture was cooled to room temperature, added with 20 mL of water, extracted with 2x20 mL of EA, and washed with 40 mL of saturated brine. The organic phase was concentrated and purified by column chromatography (PE / DCM, 0→100% DCM) to afford Compound A (205-1765 mg, 2.74 mmol, 95% yield). MS:280.07[M+H] +

[1267] Step 2: Synthesis of compound A205-2

[1268] In a 25 mL single-necked vial, compound A205-1 (767 mg, 2.75 mmol), A02-3 (1.05 g, 2.75 mmol), potassium carbonate (0.76 g, 5.49 mmol), and DMF (10 mL) were mixed and allowed to react at room temperature for 2 h. The reaction was monitored by LCMS until complete. Ethyl acetate (20 mL) was added, and the mixture was washed with saturated brine (3 x 20 mL). The organic phase was then dried and purified by column chromatography using DCM / EA (5 / 1) to afford compound A205-4 (0.80 g, 56% yield). MS: 564.09; 566.09 [M+H] +

[1269] Step 3: Synthesis of compound A205-3

[1270] Compound A205-2 (0.78 g, 1.38 mmol), zinc powder (0.45 g, 6.91 mmol), ammonium chloride (0.74 g, 13.82 mmol), DCM (15 mL), methanol (5 mL), and H2O (10 mL) were mixed and reacted at room temperature for 1.5 h. The reaction was complete after LCMS monitoring. 10 mL of water was added to the system and the layers were separated. The aqueous phase was extracted once with 10 mL of DCM, and the organic phase was washed once with 20 mL of saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated to obtain crude compound A205-3 (0.77 g, 1.44 mmol, yield: 104%). MS: 534.11, 536.11 [M+H] +

[1271] Step 4: Synthesis of compound A205-4

[1272] Compound A205-3 (770 mg, 1.44 mmol), cyanogen bromide (168 mg, 1.58 mmol), methanol (10 mL), and water (2 mL) were mixed uniformly and reacted at 70°C for 2 h. The reaction was complete after LCMS monitoring. The system was directly used for the next step without further treatment. MS: 558.11, 560.11 [M+H] +

[1273] Step 5: Synthesis of compound A205-5

[1274] After cooling the reaction system from the previous step to room temperature, NaOH (288 mg, 7.20 mmol) was added, mixed with water (8 mL) and THF (20 mL). The mixture was allowed to react at room temperature for 4 h. The reaction was complete after LCMS monitoring. 30 mL of EA was added, and the mixture was washed with 2 × 30 saturated sodium chloride solution. The mixture was dried over anhydrous sodium sulfate, filtered, and dried to give the product, compound A205-7 (750 mg, yield: 95%). MS: 545.09; 547.09 [M+H] +

[1275] Step 6: Synthesis of compound A205-6

[1276] Compound A205-7 (750 mg, 1.37 mmol), DIEA (0.45 mL, 2.74 mmol), and DCM (20 mL) were mixed uniformly. HATU (0.17 g, 1.37 mmol) was added under ice-cooling. The mixture was allowed to react at 10°C for 30 min. LCMS monitored the reaction completion. The mixture was quenched by adding 20 mL of water, extracted with 3 x 10 mL of DCM, dried over anhydrous sodium sulfate, filtered, and slurried in 10 mL of DCM to obtain compound A205-8 (430 mg, yield: 60%). MS: 527.08, 529.08 [M+H] +

[1277] Step 7: Synthesis of Compound A205

[1278] Compound A205-6 (100 mg, 0.19 mmol), 2-methyl-2,7-diazaspiro[3.5]nonane (48 mg, 0.28 mmol), Pd2(dba)3 (19 mg, 0.02 mmol), xantphos (24 mg, 0.04 mmol), sodium tert-butoxide (37 mg, 0.38 mmol), and dioxane (5 mL) were mixed and reacted at 100°C for 8 h under nitrogen atmosphere. The reaction was monitored for completion by LCMS and then sent to Prep-HPLC using a Luna C18 column, 30 x 250 mm, and a mobile phase (A: 0.1% formic acid in water, B: acetonitrile; acetonitrile increased from 17% to 50% over 20 min). Compound A205 (20 mg, 17% yield) was obtained. MS: 615.32 [M+H] +

[1279] The following final product was prepared in a similar manner to Example 205

[1280] Example 169 Synthesis of Compound A169

[1281] 1 5 , 2 6 -Difluoro-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-1 1 -Oxa-4-aza-5(2,1)-benzo[d]imidazole-1(1,2),2(1,3)-dibenzocycloundecane-3-one

[1282] Step 1: Synthesis of compound A169-1

[1283] In a 500 mL single-necked bottle, 2-fluoro-5-(methoxycarbonyl)phenylboronic acid (1.1 g, 5.56 mmol), 2-bromo-4-fluorophenol (1.27 g, 6.67 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.45 g, 0.56 mmol), potassium carbonate (2.3 g, 16.67 mmol), dioxane (15 mL), and water (3 mL) were mixed uniformly and reacted at 100°C for 3 h under nitrogen protection. The reaction was monitored by TLC to determine the completion of the reaction. The reaction mixture was cooled to room temperature, concentrated, and subjected to column chromatography with a PE:EA ratio of 10:1 to 3:1 to obtain compound A169-1 (1.20 g, 81.7% yield). Step 2: Synthesis of compound A169-2

[1284] The synthesis method of compound A169-2 is the same as that of compound A02-4, except that compound A02-1 is replaced by compound A169-1. MS of compound A169-2: 549.08, 511.08 [M+H] +

[1285] Step 3: Synthesis of compound A169-3

[1286] The synthesis method of compound A169-3 is the same as that of compound A02-5, except that compound A02-4 is replaced by compound A169-2. MS of compound A169-3: 519.10, 511.10 [M+H] +

[1287] Step 4: Synthesis of compound A169-4

[1288] The synthesis method of compound A169-4 is the same as that of compound A02-6, except that compound A02-5 is replaced by compound A169-3. MS of compound A169-4: 544.10, 546.10 [M+H] +

[1289] Step 5: Synthesis of compound A169-5

[1290] The synthesis method of compound A169-5 is the same as that of compound A02-7, except that compound A02-6 is replaced by compound A169-4. MS of compound A169-5: 530.08, 532....

Claims

1. A compound represented by formula (I), or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof: in, R3 is selected from M1, M3, M4, M7, M8 and M9 are independently selected from CR c , CR c R c , N or NR c ; M2, M5, M6, M 10 Independently selected from absence, CR c R c 、-CR c R c -CR c R c - or NR c ; L1, L2 are selected from chemical bonds, -CR h R i -、-NR h -, -O-, -S-, -S(=O)-, -S(=O)2-, -C(=O)-, -NR h -C(O)-, -C(O)-NR h -, -OC(=O)- or -C(=O)O-; L3 is selected from a chemical bond, -S-, -S(=O)-, -S(=O)2-, -O-, -NR h -、-CR h R i -、 or C 3-5 Cycloalkylene; wherein the C 3-5 Cycloalkylene is optionally substituted with one or more R h replace; Ring A and Ring B are independently selected from C 6-14 Aryl, C 3-14 carbocyclyl, 5-14 membered heteroaryl or 3-14 membered heterocyclyl; Each R a 、R b The same or different, each independently selected from H, deuterium, halogen, -CN, oxo, NO2, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、-OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)2R e 、-S(O)(=NRe)R f 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f 、-N(R e )S(O)2R f 、-C(O)OR e 、-OC(O)R f 、-OC(O)OR g 、C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C0-6 alkylene-C 3-14 Carbocyclic group, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-3-14 membered heterocyclic group or -C0-6 alkylene-5-14 membered heteroaryl; wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C0-6 alkylene-C 3-14 Carbocyclic group, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-3-14 membered heterocyclic group, -C0-6 alkylene-5-14 membered heteroaryl, R e 、 R f and R g Optionally replaced by one or more hydrogen, deuterium, halogen, CN, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, -OR h 、-NR h R i , substituted or unsubstituted -C0-6 alkylene-C3- 14 Carbocyclic group, substituted or unsubstituted -C0-6 alkylene-3-14 membered heterocyclic group, -C(O)OR h 、-C(O)NR h R i replace; Each R1 and R2 are independently selected from R h ;or R1 and R2 together with the atoms to which they are attached form C(O), C=CR h R i 、C=NR h , 3-14 membered heterocyclic group or C 3-14 Carbocyclic group; wherein the 3-14 membered heterocyclic group or C 3-14 The carbocyclyl group is optionally substituted by one or more R h replace; R4 and R5 are selected from H, deuterium, halogen, -CN, NO2, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、-OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f 、-N(R e )S(O)2R f 、-N=S(=O)R c‘ R c” 、-C(O)OR e 、-OC(O)R f 、-OC(O)OR g 、 C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C0-6 alkylene-C 3-14 Carbocyclic group, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-3-14 membered heterocyclic group or -C0-6 alkylene-5-14 membered heteroaryl; wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -C0-6 alkylene-C 3-14 Carbocyclic group, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-3-14 membered heterocyclic group, -C0-6 alkylene-5-14 membered heteroaryl, R e 、R f and R g Optionally, one or more R h replace; or Each R c The same or different, each independently selected from H, deuterium, halogen, CN, NO2, oxo, C 1-6 Alkyl, C2-6 alkenyl, C2-6 alkynyl, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-5-14 membered heteroaryl, -C0-6 alkylene-C3- 14 Carbocyclic group, -C0-6 alkylene-3-14 membered heterocyclic group, -OR e 、-NR e R f 、-SR e 、-C(O)R e 、-N(R e )C(O)R f 、-C(O)NR e R f 、-N(R e )C(O)OR f 、-OC(O)NR e R f 、-N(R e )C(O)NR f R g 、-S(O)R e 、-S(O)(=NRe)R f 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-N(R e )S(O)R f 、-N(R e )S(O)2R f 、-C(O)OR e 、-OC(O)R f OR-OC(O)OR g ; Wherein, the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-5-14 membered heteroaryl, -C0-6 alkylene-C3- 14 Carbocyclic group, -C0-6 alkylene-3-14 membered heterocyclic group, R c‘ 、R c” 、R e 、R f and R g Optionally, one or more R h 、-OR h 、-NR h R i 、-C(O)OR h 、-C(O)NR h R i 、-NR h C(O)R i replace; R c’ and R c” are independently selected from H, C 1-6 Alkyl or C 1-6 haloalkyl; or R c’ and R c” Together with the atoms to which they are attached, they form a 5-7 membered heterocyclic ring, which is optionally substituted by one or more R h replace; R e 、R f 、R g 、R h 、R i are independently selected from hydrogen, deuterium, halogen, CN, OH, NH2, -COOH, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 3-14 Cycloalkyl, -O-3-14 heterocyclic group, -S-3-14 heterocyclic group, -SC 3-14 Cycloalkyl, -SC 1-6 Alkyl, -CONH2, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6 Alkynyl, -S(O)-C 3-14 Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NH2, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -CHO, -C(O)-C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-5-14 membered heteroaryl, -C 0-6 Alkylene-C 3-14 Carbocyclic or -C 0-6 Alkylene-3-14 membered heterocyclic group; wherein the -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 3-14 Cycloalkyl, -O-3-14 heterocyclic group, -S-3-14 heterocyclic group, -SC 3-14 Cycloalkyl, -SC 1-6 Alkyl, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6 Alkynyl, -S(O)-C 3-14 Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -C(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -C0-6 alkylene-C 6-14 Aryl, -C0-6 alkylene-5-14 membered heteroaryl, -C 0-6 Alkylene-C 3-14 Cycloalkyl and -C 0-6 Alkylene-3-14 membered heterocyclic radicals are optionally replaced by one or more hydrogen, deuterium, halogen, CN, OH, NH2, -COOH, oxo, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -COO(C 1-6 alkyl), -CONH(C 1-6 alkyl), -CON(C 1-6 Alkyl)2, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 2-6 Alkenyl, -S(O)2-C 2-6 Alkenyl, -S(O)-C 2-6 Alkynyl, -S(O)2-C 2-6 Alkynyl, -S(O)-C 3-14 Cycloalkyl, -S(O)2-3-14 heterocyclyl, -S(O)NH2, -S(O)NHC 1-6 Alkyl, -S(O)N(C 1-6 Alkyl)2, -C 0-6 Alkylene-NHC(=O)C 1-6 Alkyl, -C 0-6 Alkylene-NHC(=O)C 1-6 Haloalkyl, -C 0-6 Alkylene-NHC(=O)C 2-6 Alkenyl, substituted or unsubstituted -C 0-6 Alkylene-C 3-14 Carbocyclyl, substituted or substituted-C 0-6 Alkylene-3-14 membered heterocyclic group substitution; m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; r is 0, 1, 2, 3, 4, or 5; t is 0, 1, 2, or 3.

2. The compound according to claim 1, or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form, characterized in that: L1 is selected from a chemical bond, -CH2-, -NH-, -O-, -S-, -C(=O)-, -NHC(=O)-, -C(=O)NH-, -OC(=O)-, or -C(=O)O-.

3. The compound according to claim 1 or 2, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L1 is selected from a chemical bond, -CH2- or -NHC(=O)-.

4. The compound according to any one of claims 1 to 3, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L1 is selected from -CH2-.

5. The compound according to any one of claims 1 to 4, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L2 is selected from a chemical bond, -O-, -S-, -NH- or -C(=O)-.

6. The compound according to any one of claims 1 to 5, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L2 is selected from a chemical bond or -O-.

7. The compound according to any one of claims 1 to 6, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L3 is selected from chemical bonds, -NH-, -O-, -S-, -CH2-, 8. The compound according to any one of claims 1 to 7, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: L3 is a chemical bond or -NH-.

9. The compound according to any one of claims 1 to 8, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from C 8-14 Bicyclic aryl or 7-14 membered bicyclic heteroaryl.

10. The compound according to any one of claims 1 to 9, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from 11. The compound according to any one of claims 1 to 8, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from C 3-8 Monocyclic carbocyclic group, 3-8 membered monocyclic heterocyclic group, C 6-8 a monocyclic aryl group or a 5- to 8-membered monocyclic heteroaryl group.

12. The compound according to any one of claims 1 to 8 and 11, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from 13. The compound according to any one of claims 1 to 8 and 11, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from a benzene ring or a 5-7 membered heteroaryl ring.

14. The compound according to any one of claims 1 to 8, 11, and 13, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt, or deuterated form thereof, characterized in that: Ring A is selected from a benzene ring or a 6-membered heteroaryl ring.

15. The compound according to any one of claims 1-8, 11-14, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring A is selected from 16. The compound according to any one of claims 1 to 15, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring B is a 5- to 7-membered monocyclic heteroaryl group, an 8- to 10-membered bicyclic heteroaryl group, or an 8- to 10-membered bicyclic heterocyclyl group.

17. The compound according to any one of claims 1 to 16, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring B is a benzene ring, pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, pyrrole, thiophene, imidazole, oxazole, isoxazole, furan, thiazole or isothiazole.

18. The compound according to any one of claims 1 to 16, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring B is a 5-membered or 6-membered monocyclic heteroaryl group containing 1-3 independently selected N atoms, a 5-membered or 6-membered bicyclic heteroaryl group containing 1-4 independently selected N atoms, a 5-membered or 6-membered bicyclic heteroaryl group containing 1-4 independently selected N atoms, or a 5-membered or 6-membered bicyclic heterocyclyl group containing 1-4 independently selected N atoms.

19. The compound according to any one of claims 1 to 16 and 18, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring B is 20. The compound according to any one of claims 1-16, 18-19, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: Ring B is 21. The compound according to any one of claims 1 to 20, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R a H, halogen, –CN, -NH2, -OH, -C(=O)OH, -C(=O)NH2, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 Alkyl; wherein the C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 The alkyl group is optionally substituted with one or more halogen, -CN, -NH2, -OH.

22. The compound according to any one of claims 1 to 21, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R a H, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, halogen, -CN, C 3-6 Cycloalkyl, amino, cyano substituted C 1-3 Alkyl, -OH, -C(=O)OH, -C(=O)NH2, -NH-C(O)-C 1-6 Alkyl or -C(O)C 1-6 alkyl.

23. The compound according to any one of claims 1 to 22, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R a H, D, F, Cl, Br, –CN, -NH2, C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 2-4 Alkynyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl or cyano substituted C 1-3 alkyl.

24. The compound according to any one of claims 1 to 23, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R a For H, D, CH3, CD3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -C≡CH, OCH3, CF3, F, Cl, -NH2 or -CN.

25. The compound according to any one of claims 1 to 23, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R a is H or CH3.

26. The compound according to any one of claims 1 to 24, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R1 or R2 are independently selected from H, C 1-6 Alkyl, deuterated C 1-6 Alkyl, hydroxyl, C 1-6 Haloalkyl, halogen, amino, C 1-6 Alkoxy or C 1-6 Halogenated alkoxy.

27. The compound according to any one of claims 1 to 26, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R1 or R2 are independently selected from H or C 1-3 alkyl.

28. The compound according to any one of claims 1 to 25, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R1 and R2 together with the atoms to which they are attached form 29. The compound according to any one of claims 1 to 28, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R4 is H, halogen, cyano, -NH2, -OH, -C(=O)OH, -C(=O)NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl, -C(O)C 1-6 Alkyl, C 6-10 aryl, 5-10 membered heterocyclic group or 5-10 membered heteroaryl; wherein, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, -NH-C(O)-C 1-6 Alkyl, -C(O)C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heterocyclyl and 5-10 membered heteroaryl are optionally substituted by one or more R h replace.

30. The compound according to any one of claims 1 to 29, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: R4 is H, halogen, -NH2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-6 Cycloalkyl, cyano or 8-10 membered heterocyclic group; wherein the 8-10 membered heterocyclic group can be optionally replaced by -C(O)-C 2-4 Alkenyl substitution.

31. The compound according to any one of claims 1 to 30, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R4 is H, CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -C≡CH, OCH3, CF3, F, Cl, -NH2, -CN or 32. The compound according to any one of claims 1 to 31, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R4 is H or 33. The compound according to any one of claims 1 to 32, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R4 is H.

34. The compound according to any one of claims 1 to 33, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R5 is H, halogen, -NH2, -OH, -C(=O)OH, -C(=O)NH2, -N=S(=O)(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 1-6 Alkylene cyano, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-7 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; the -NH2, -OH, -C(=O)OH, -C(=O)NH2, -N=S(=O)(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, C 1-6 Alkylene cyano, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-7 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R h replace.

35. The compound according to any one of claims 1 to 34, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R5 is H, halogen, C 1-6 Alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 1-6 Alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups are optionally substituted with one or more OH, NH2, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, -S(O)2-C 1-6 Alkyl, C 1-6 Alkyl-S(O)2-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 substituted.

36. The compound according to any one of claims 1 to 35, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R5 is H, F, Cl, NH2, CH3, 37. The compound according to any one of claims 1 to 36, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R5 is H.

38. The compound according to any one of claims 1 to 37, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R b H, D, halogen, -CN, -OH, -NH2, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, -SC 1-6 Alkyl, -S(=O)-CH3, -S(=O)2-C 1-6 Alkyl, -S(=O)2-C 3-6 Cycloalkyl or -O-3-6 membered heterocyclic group.

39. The compound according to any one of claims 1 to 38, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R b is H, D, F, Cl, -OCH3, CH3, CD3, CF3, CN, NH2, -S-CH3, -S(=O)-CH3, 40. The compound according to any one of claims 1 to 39, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: R b H, deuterated C 1-3 Alkyl or C 1-3 Alkyl; preferably, R b is H or CH3.

41. The compound according to any one of claims 1 to 40, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R3 is 42. The compound according to any one of claims 1 to 41, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R3 is 43. The compound according to any one of claims 1 to 42, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R c H, deuterium, halogen, CN, oxo, OH, -NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, -C(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -COOH, -C 0-6 Alkylene-CONH2, -NHC(O)-C 2-6 Alkenyl, -C 1-6 Alkylene NHC(O)-C 2-6 Alkenyl, -S(=O)2-C 1-6 Alkyl, -S(=O)(=NH)-C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, phenyl, 5-6 membered heteroaryl or 3-11 membered heterocyclic group; wherein the OH, -NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, -C(O)-C 1-6 Alkyl, -C(O)-C 2-6 Alkenyl, -COOH, -C 0-6 Alkylene-CONH2, -NHC(O)-C 2-6 Alkenyl, -C 1-6 Alkylene NHC(O)-C 2-6 Alkenyl, -S(=O)2-C 1-6 Alkyl, -S(=O)(=NH)-C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, phenyl, 5-6 membered heteroaryl and 3-11 membered heterocyclyl may be optionally substituted with one or more halogen, OH, CN, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -NH2, -COOH, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -CONH2, -CONH(C 1-6 alkyl), -CON(C 1-6 alkyl)2, -CONH(C 2-6 alkenyl), -CON(C 2-6 alkenyl)2, -CONH(C 2-6 Alkynyl), -CON(C 2-6 Alkynyl)2, -S(=O)2-C 1-6 Alkyl, substituted or unsubstituted -CO-3-6 membered heterocyclic group, -OC 1-6 Haloalkyl, -OC(=O)NH2, -OCONH(C 1-6 alkyl) or -OCON(C 1-6 alkyl)2 substituted.

44. The compound according to any one of claims 1 to 43, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R c H, D, CH3, CD3, CH2CH3, CH(CH3)2, -C(CH3)3, -OH, F, Cl, oxo, NH2, 45. The compound according to any one of claims 1 to 44, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R3 is 46. ​​The compound according to any one of claims 1 to 45, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: m is 0, 1 or 2.

47. The compound according to any one of claims 1 to 46, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: n is 0, 1 or 2.

48. The compound according to any one of claims 1 to 47, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: r is 2, 3 or 4.

49. The compound according to any one of claims 1 to 48, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: t is 0, 1, or 3.

50. The compound according to any one of claims 1 to 49, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: The compound of formula (I) is selected from the compounds of formula (II) or formula (III) shown below: in, M1-M in the compounds of formula (II) and formula (III) 10 , L1, L2, L3, Ring B, R a 、R b , R1, R2, R4, m, n and r are as defined in any one of claims 1-49.

51. The compound according to any one of claims 1 to 49, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, characterized in that: The compound of formula (I) is selected from the compound of formula (IV) shown below: in, M1-M in the compound of formula (IV) 10 、R a 、R b , n and r are as defined in any one of claims 1-49.

52. The compound according to any one of claims 1 to 49, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: The compound of formula (I) is selected from the compounds of formula (V) or formula (VI) shown below: in, Q1, Q2, Q3 and Q4 are independently selected from CR b or N; Q5 and Q6 are independently selected from N or C; M1-M in the compound of formula (V) or formula (VI) 10 , L1, L2, Ring A, R a 、R b , R1, R2, R4, m and r are as defined in any one of claims 1-49.

53. The compound according to any one of claims 1 to 49, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: The compound of formula (I) is selected from the compounds of formula (VII) or formula (VIII) shown below: in, Q1, Q2, Q3 and Q4 are independently selected from CR b or N; Q5 and Q6 are independently selected from N or C; M1-M in the compound of formula (VII) or formula (VIII) 10 , L1, L2, Ring A, R a 、R b , R1, R2, R4, R5, m and r are as defined in any one of claims 1-49.

54. The compound according to claim 1, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, wherein: The compound is selected from: 1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,7-diazaspiro[3.5]nonan-7-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridinyl-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(2-acryloyl-2,7-diazaspiro[3.5]non-7-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (E)-5 6 -(2-Acryloyl-2,9-diazaspiro[5.5]undec-9-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (E)-1 1 , 2 6 -Dimethyl-5- 6 -(2-methyl-2,9-diazaspiro[5.5]undec-9-yl)-5 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2,2,2-trifluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2-(9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-5-nitro- 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)acetonitrile; 2 6 -Methoxy-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(9-ethyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrimidin-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-nitrogen Hetero-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -Chloro-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -cyclopropyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -Amino-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -ethynyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -ethyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolecycloundecyl-2 6 -nitrile; 2 6 -Isopropyl-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3-azaspiro[5.5]undec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(7-fluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(7-hydroxy-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (Z)-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 , 1 5 , 1 6 , 1 7 -Tetrahydro-5- 1 H-4-aza-1(3,5)-[1,2,3]triazolo[1,5-a]pyrazine-5(2,1)-benzo[d]imidazo-2(2,4)-pyridinylcyclononane-3-one; 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 4 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(3,4)-triazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-2-oxo-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-4-aza-5(2,1)-benzo[d]imidazo-1(7,1)-imidazo[1,2-b]pyrazol-2(2,4)-pyridocyclodecane-3-one; (1 3 Z, 1 4 E, 5 2 Z)-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 2 , 5 3 -Dihydro-5 1 H-9-oxa-4-aza-1(3,5),5(2,1)-dipyrazolo[1,5-a]pyrido-2(2,4)-pyridocyclononane-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(8-methyl-2,8-diazaspiro[5.5]undec-2-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(9-ethyl-2,9-diazaspiro[5.5]undec-2-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(3-methyl-3,9-diazaspiro[5.6]dodec-9-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 6 -(9-(dimethylamino)-3-azaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-2,9-diazaspiro[5.5]undec-2-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazolo-2(1,3)-benzocycloundecan-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 6 -nitrile; 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 2 6 -Methoxy-1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one; 1 5 -Fluorine-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one; 1 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(3,2)-pyrrolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(3,2)-pyrrolocycloundecane-1 5 -nitrile; (E)-5 6 -(9-cyclopentyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; (E)-5 6 -(9-acetyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; (E)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-5- 2 , 5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-cyclobutyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(1-fluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; (Z)-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-2(7,5),5(2,1)-dipyrazolo[1,5-a]pyrido-1(4,5)-pyrazolocycloundecan-3-one; 1 1 ,2 6 -Dimethyl-5- 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 2 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(7,5)-indolo-1(4,5)-pyrazolocycloundecan-3-one; (Z)-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-2(8,6),5(2,1)-diimidazo[1,2-a]pyrido-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 1 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 2 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(7,5)-indolo-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(1,1-difluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(7,7-difluoro-9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-methyl-2-azabicyclo[2.2.1]heptane-5-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)- Pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyl-3-azabicyclo[3.1.1]heptane-6-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; (E)-1 1 ,2 6 -Dimethyl-5- 6 -(9-(1-methylpiperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 2 ,5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(5-methyl-5-azaspiro[2.5]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(octahydroindolizin-7-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2-cyclopropylethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxepan-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(4-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(4-hydroxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(4-methoxy-4-methylpentan-2-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H,5 3 H-11-oxa-4-aza-5(2,3)-imidazo[4,5-b]pyridine-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(8-oxabicyclo[3.2.1]octan-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2-hydroxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 2 6 -Fluorine-2 5 -Methoxy-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 2 6 -Fluorine-1 1 , 2 5 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 2 5 ,2 6 -Difluoro-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzoic acid cycloundecane-3-one; 5 7 -Chloro-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 ,9,9-tetramethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -Fluorine-1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 5 7 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 , 5 5 -Trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2-(hydroxymethyl)cyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2-hydroxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-Hydroxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-hydroxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2-hydroxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(4-isopropoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one 5 6 -(9-(3-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(4-ethoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazo-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-Hydroxycyclopentyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(1-cyclopropylpiperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(1-(oxetane-3-yl)piperidin-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(3'-oxa-3,9-diaza[3,9'-bispiro[5.5]undecane]-9-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 -(cyclopropylsulfonyl)-2- 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(tetrahydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 2 6 -Fluorine-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 5 -nitrile; 1 5 -Methoxy-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(7,5)-benzofurancycloundecan-3-one; 1 5 -Fluorine-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one; 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -Fluoro-11-methyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 3-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3-azaspiro[5.5]undecane-9-carboxylic acid; 9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)- Pyridine-1(4,5)-pyrazolocycloundecane-5-one 6 -yl)-3,9-diazaspiro[5.5]undecane-3-carboxamide; 2-(9-(1 1 , 2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)cyclopentane-1-carboxylic acid; 2 6 -Fluoro-5 5 -Methoxy-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 1 5 , 2 6 -Difluoro-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-1 1 -Oxa-4-aza-5(2,1)-benzo[d]imidazol-1(1,2),2(1,3)-dibenzocycloundecane-3-one; 2 6 -Fluorine-1 1 -methyl-5 6 -(9-(oxepan-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-1(4,5)-pyrazole-2(1,3)-benzocycloundecane-2 5 -nitrile; 2 5 -Chloro-2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 5 5 -Methoxy-1 1 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 2 5 -Amino-2 6 -Fluorine-1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-11H,5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 5 5 -Methoxy-1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 5 5 -Chloro-2 6 -Fluorine-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-26-fluoro-1 1 , 5 5 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 -Trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 2 6 -Fluorine-1 1 , 5 5 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-3-one; 1 1 , 2 6 , 5 5 -Trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-5- 5 -Fluorine-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -Chloro-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -ethynyl-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -Amino-1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -(dimethylamino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -((2-methoxyethyl)(methyl)amino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -Hydroxy-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -cyclobutoxy-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 5 -nitrile; 5 5 -(cyclobutylamino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 5 -((2-(dimethylamino)ethyl)amino)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 5 - methyl carboxylate; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-nitropropane 5 -formamide; 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(tetrahydro-2H-thiopyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methylsulfonyl)-3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methylsulfonyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(S-methylsulfonylimino)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 4 ,1 5 -Difluoro-2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undecen-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; 1 1 ,2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(Oxa-3-amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; (R)-1 1 ,2 6 ,7-trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 9-(1 1 ,2 6 -Dimethyl-3-oxo-1 1 H, 5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-5-(2,1)-benzo[d]imidazole 6 -yl)-3,9-diazaspiro[5.5]undecane-3-carbaldehyde; 1 1 ,2 6 -Dimethyl-5- 6 -(9-(pyrrolidin-1-yl)-3-azaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-2-one; 1 1 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyrazol-2(1,3)-benzocycloundecan-2-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-(methylsulfonyl)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 ,2 2 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(4,6)-pyrimidin-1(4,5)-pyrazolocycloundecan-3-one; 2 5 -Methoxy-1 1 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 2 5 -Fluorine-1 1 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecyl-3-one; 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(6,7)-furo[3,2-b]pyridine-5(2,1)-benzo[d]imidazol-2(2,4)-pyridoylundecyl-3-one; 2 6 -methyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one; 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-1 5 -carbonitrile; 1 5 -Amino-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-phenylcycloundecane-3-one; 2 6 -methyl-1 2 -(methylthio)-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one; 2 6 -methyl-1 2 -(methylsulfonyl)-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecyl-3-one; 1 2 -Chloro-2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazolyl[5.5]undecane-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one; 1 2 ,1 6 ,2 6 -Trimethyl-5 6 -(9-(oxa-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one; 1 2 ,2 6 -Dimethyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-5-(9- ... 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(5,4)-pyrimidin-2-(2,4)-pyridocycloundecan-4-one; 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(2,4)-pyrimidin-2(2,4)-pyridocycloundecan-3-one; 5 6 -(9-(3,3-difluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 1 1 ,2 6 -Dimethyl-5- 6 -(9-(thiophen-3-yl)-3,9-diazaspiro[5.5]undec-3-yl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 1 1 ,2 6 -Dimethyl-5- 6 -(9-(1-oxidothiophen-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(1,1-dioxidothiophene-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(7-hydroxy-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(7-methoxy-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(7-fluoro-9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(3,4)-quinolin-5(2,1)-benzo[d]imidazol-2(2,4)-pyridocycloundecan-3-one; 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-1(8,7)-quinolin-5(2,1)-benzo[d]imidazol-2(2,4)-pyridocycloundecan-3-one; 2 6 -methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(3,4)-pyridazin-2(2,4)-pyridocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(3-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecane-3-one; 5 6 -(9-(3,3-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(5-oxaspiro[2.5]octan-8-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(3-fluorotetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2,3,5,6-tetramethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 5 6 -(9-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 -Dimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-((2S)-2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-((2R)-2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(2-methyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(2-(methylsulfonyl)ethyl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyrido-1(4,5)-pyrazolocycloundecan-3-one; (R)-5 5 -(3-(dimethylamino)pyrrolidin-1-yl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(3-((methylsulfonyl)methyl)azetidin-1-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(tetrahydrofuran-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 5 -cyclopropyl-1 1 , 2 6 -dimethyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 5 -(1,1-dioxotetrahydro-2H-thiopyran-4-yl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 5 -(2-ethoxyethyl)-1 1 , 2 6 -dimethyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 11-cyclopropyl-26-methyl-56-(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(piperidin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(1-methylpiperidin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -(1-(methylsulfonyl)piperidin-4-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 ,2 6 ,7-trimethyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-5- 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-1 1 H,51H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluoro-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluoro-5 6 -(9-(4-methoxycyclohexyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluoro-5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluoro-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 ,7-trimethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-(3-methoxycyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 5 -((2-(methylsulfonyl)ethyl)amino)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecan-3-one; (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11- Oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-(2-fluoroethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 , 2 6 , 5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 ,7-tris(methyl-d3)-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 5 5 -(3-hydroxy-3-methylbutyl)-1 1 , 2 6 -Dimethyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 -Dimethyl-5- 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 2 6 -methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-4-aza-5(2,1)-benzo[d]imidazole-1(3,4),2(2,4)-bipyridocycloundecyl-3-one; (E)-1 1 ,2 6 -Dimethyl-5- 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 2 ,5 3 -Dihydro-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolidinecyclodecane-3-one; 5 5 -Fluorine-1 1 , 2 6 -Dimethyl-5- 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; 1 1 , 2 6 ,5 5 -Trimethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(methyl-d3)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 ,2 6 ,7-trimethyl-5 5 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; (R)-5 5 -Fluorine-1 1 , 2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-1 1 , 2 6 , 5 5 ,7-tetramethyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazolocycloundecyl-3-one; (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H,5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocyclodecane-3-one; (R)-5 5 -Amino-1 1 ,2 6 ,7-trimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(4,5)-pyrazolocycloundecan-3-one; (7R)-5 6 -(9-(4-methoxy-4-methylpentan-2-yl)-3,9-diazaspiro[5.5]undec-3-yl)-1 1 ,2 6 ,5 5 ,7-tetramethyl-1 1 H, 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(4,5)-pyrazole Cycloundecane-3-one; (R)-2 6 ,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecan-3-one; (R)-2 6 ,7-dimethyl 5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocycloundecan-3-one; (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocyclohexen-3-one; (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 ,7-dimethyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-1(4,5)-pyridazin-2(2,4)-pyridocyclohexen-3-one; (R)-2 6 ,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 ,7-dimethyl 5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-7-Methyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-2 6 -Chloro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -methoxy-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -ethyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -isopropyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-1 5 -Fluorine-2 6 ,7-dimethyl 5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-1 5 -Fluorine-2 6 ,7-dimethyl 5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-1 5 -Fluorine-2 6 ,7-dimethyl 5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-1 4 ,1 5 -Difluoro-2 6 ,7-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-7-Methyl-5- 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -(trifluoromethyl)-5-( 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -cyclopropyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -ethynyl-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-1 5 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -carbonitrile; (R)-1 4 ,1 5 -difluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-1 4 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -carbonitrile; (R)-7-Methyl-5- 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-ethyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4- Aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (7R)-7-methyl-3-oxo-5- 6 -(9-(tetrahydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-7-methyl-3-oxo-5- 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (7R)-5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (7R)-5 6 -(9-(2-oxabicyclo[2.2.1]heptane-5-yl)-3,9-diazaspiro[5.5]undecane-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-(2-(9-(2 6 -cyano-7-methyl-3-oxo-51H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)ethyl)carbamic acid methyl ester; (R)-3-(9-(2 6 -cyano-7-methyl-3-oxo-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-5-(2,1)-dihydro-1-nitro-2-nitro-1 ... 6 -yl)-3,9-diazaspiro[5.5]undec-3-yl)-N,N-dimethylpropionamide; (R)-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(3-cyclopropyloxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-7-Methyl-5- 6 -(9-(3-(methylsulfonyl)propyl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(2-(dimethylamino)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (7R)-7-Methyl 5- 6 -(9-(2-methyloxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(3-fluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(3,3-difluorocyclobutyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-7-methyl-3-oxo-5- 6 -(9-(2-(trifluoromethoxy)ethyl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(cyanomethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; 9,9-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-3-oxo-5- 1 H-11-oxo-4-aza-5(2,1)-benzo[d]imidazole-2(2,4)-pyridine-1(1,2)-benzocycloundecane-2 6 -nitrile; (R)-5 6 -(9-(3-(azetidin-1-yl)-3-oxopropyl)-3,9-diazaspiro[5.5]undec-3-yl)-2 6 -Chloro-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-5 6 -(9-cyclopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-7-methyl-5 6 -(9-(oxetane-3-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-7-methyl-5 6 -(9-(tetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (7R)-2 6 -Chloro-5 6 -(9-((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-1 5 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-5 6 -(9-(2-methoxyethyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; 2 6 -Chloro-9,9-dimethyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-1 4 -fluoro-7-methyl-5 6 -(9-methyl-3,9-diazaspiro[5.5]undec-3-yl)-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecane-3-one; (R)-2 6 -Chloro-5 6 -(9-(3-methoxypropyl)-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecan-3-one; or (R)-2 6 -Chloro-5 6 -(9-isopropyl-3,9-diazaspiro[5.5]undec-3-yl)-7-methyl-5 1 H-11-oxa-4-aza-5(2,1)-benzo[d]imidazol-2(2,4)-pyridin-1(1,2)-benzocycloundecan-3-one.

55. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises a therapeutically effective amount of at least one compound according to any one of claims 1 to 54, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated substance thereof and at least one pharmaceutically acceptable excipient.

56. Use of a compound according to any one of claims 1 to 54, or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated form thereof, or the pharmaceutical composition according to claim 55 in the preparation of an anti-tumor drug; preferably, the anti-tumor drug is used for the following conditions: head and neck cancer, melanoma, bladder cancer, esophageal cancer, anaplastic large cell lymphoma, renal cell carcinoma, breast cancer, colorectal cancer, ovarian cancer, cervical cancer, pancreatic cancer, glioma, glioblastoma, prostate cancer, leukemia, lymphoma, non-Hodgkin's lymphoma, gastric cancer, lung cancer, hepatocellular carcinoma, gastrointestinal stromal tumor, thyroid cancer, bile duct cancer, endometrial cancer, multiple myeloma or mesothelioma.

57. The use according to claim 56, characterized in that The tumor is a malignant tumor carrying an EGFR gene mutation: preferably, the EGFR gene mutation is selected from one or more of an EGFR Del19 gene mutation, an EGFR L858R gene mutation, an EGFR T790M gene mutation, and an EGFR C797S gene mutation.

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