Substituted [1,2,4]triazolo-[4,3-c]pyrimidine compounds and use thereof as EED inhibitors

Abstract

The present invention relates to a compound of formula (X) or a tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutical composition containing the compound. Uses of the same are disclosed herein in the manufacture of a medicament for tumor immunization, or the treatment and / or prevention of an EED- and / or PRC2-mediated disease. [Image disponible dans le document PDF, Image available in the PDF document]

Description

Substituted [1,2,4]triazolo-[4,3-c]pyrimidine compounds and use thereof as EED inhibitors FIELD OF THE INVENTION

[0001] The present disclosure belongs to the field of medicinal chemistry, and in particular, relates to a new class of EED inhibitors, preparation methods thereof, and pharmaceutical compositions comprising the class of compounds. The class of compounds can be used for the treatment of tumor-related diseases, such as breast cancer, prostate cancer, liver cancer, sarcoma, gastric cancer, diffuse large B-cell lymphoma, follicular lymphoma, and melanoma. BACKGROUND OF THE INVENTION

[0002] Polycombgroup protein (PcG) is an important family of epigenetic regulators, wherein dysregulation of the members has been found in a variety of tumors. One of important members, Polycomb repressive complex 2 (PRC2), is a protein methyltransferase complex that can methylate the lysine at 27th position of histone H3 (H3K27) near the promoter region of downstream target genes, thereby inhibiting the transcriptional activity of target genes, and playing an important role in development and tissue differentiation and regeneration. The PRC2 complex contains three core subunits: EZH2, EED and SUZ12, all of which are required for PRC2 activity. EZH2 can directly binds to the methyl group donor S-adenosylmethione (SAM) and is an enzymatic subunit; EED can bind to trimethylated H3K27 (H3K27me3) to allosterically activate EZH2, and is an allosteric subunit; and SUZ12 assists in the formation and activity of the complex. EZH1 is a homologous protein of EZH2, and can also participate in the formation of PRC2 but with weak enzymatic activity. In recent years, studies have found that the expressions of EZH2, EED and SUZ12 are up-regulated in a variety of tumors, including but not limited to breast cancer, prostate cancer, liver cancer, sarcoma, and gastric cancer. Activating mutations in EZH2 have also been found in tumors such as diffuse large B lymphoma, follicular lymphoma, and melanoma. Reducing the level and activity of PRC2 by siRNA or PRC2 inhibitor can inhibit the proliferation of tumors such as lymphoma, which reveals that abnormal PRC2 activity is the cause of cancer occurrence and metastasis, and PRC2 can be used as a drug target for treatment. In addition, many studies have reported that PRC2 is also closely related to immune responses mediated by T cells and NK cells. Therefore, PRC2 is a promising drug target for the treatment of lymphoma and other tumors.

[0003] At present, there are mainly two drug development mechanisms targeting PRC2: the first is to compete with SAM to bind to EZH2 to exert an inhibitory effect, wherein EPZ-6438 (Epizyme, FDA approved), CPI-1205 (Constellation, Phase II clinical trial) and DS-3201 (Dailchi, Phase II clinical trial) have entered into clinical trials; and another is to allosterically inhibit the activity of PRC2 by targeting EED, wherein only one case, MAK683 (Novartis, Phase I / II clinical trial), has entered into clinical trials. The published tool compounds are A-395 (Abbott) and EED226 (Novartis), which can overcome the resistance problem of the first class of inhibitors due to different binding pockets. To sum up, the PRC2 complex is a proven and promising drug target, and the PRC2 inhibitor targeting EED is still in a relatively early stage of development at present. In-depth research on inhibitors of this target is beneficial to the development of new drugs related to the target, which has broad application value. SUMMARY OF THE INVENTION

[0004] Therefore, the object of the present disclosure is to provide a new class of small molecule EED inhibitors, which can be used for the treatment and / or prevention of EED- and / or PRC2-mediated diseases.

[0005] In this regard, the present disclosure adopts the following technical solutions:

[0006] In one aspect, the present disclosure relates to a compound of formula (X), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (X) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; or <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form <com:Math><semantics>−(CH2)pY<annotation encoding="application / x-tex">-(CH_2)_pY< / annotation>< / semantics>< / com:Math> -, <com:Math><semantics>−Y(CH2)p<annotation encoding="application / x-tex">-Y(CH_2)_p< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−Y(CH2)pZ<annotation encoding="application / x-tex">-Y(CH_2)_pZ< / annotation>< / semantics>< / com:Math>- group; wherein p is 1, 2, 3, 4 or 5; Y is selected from O, S, NH or chemical bond; Z is selected from O, S, NH or chemical bond; <com:Math><semantics>ℝ*<annotation encoding="application / x-tex">\mathbb{R}^{*}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is selected from <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R3′)−C(O)−<annotation encoding="application / x-tex">-N(R_3')-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−C(O)−<annotation encoding="application / x-tex">-O-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−N(R)−<annotation encoding="application / x-tex">-S(O)_q-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−O−<annotation encoding="application / x-tex">-S(O)_q-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−<annotation encoding="application / x-tex">-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S−<annotation encoding="application / x-tex">-S-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−<annotation encoding="application / x-tex">-C(O)-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(R″)<annotation encoding="application / x-tex">N(R'')< / annotation>< / semantics>< / com:Math>-, -C<com:Sub>1-4< / com:Sub> alkylene- or -C<com:Sub>2-4< / com:Sub> alkenylene-; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; <com:Math><semantics>R**<annotation encoding="application / x-tex">R^{**}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; q is 0, 1 or 2; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a< / com:Sub>R<com:Sub>b< / com:Sub>, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-OR<com:Sub>a< / com:Sub>, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>3-7< / com:Sub> cycloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-3- to 10-membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>6-10< / com:Sub> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-; or, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; wherein R₃ is optionally substituted by one or more substituent groups selected from H, D, halogen, CN, OH, =0, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>3-7< / com:Sub> cycloalkyl, 4- to 7-membered heterocyclyl, C<com:Sub>6-10< / com:Sub> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> CA haloalkoxy, -O-C<com:Sub>3-7< / com:Sub> cycloalkyl, -O-4- to 7-membered heterocyclyl, -O-C<com:Sub>6-10< / com:Sub> aryl, -O-5- to 10-membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−S(O)q−C3−7<annotation encoding="application / x-tex">-S(O)_q-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−S(O)q−4<annotation encoding="application / x-tex">-S(O)_q-4< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−S(O)q−C6−10<annotation encoding="application / x-tex">-S(O)_q-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−S(O)q−1<annotation encoding="application / x-tex">-S(O)_q-1< / annotation>< / semantics>< / com:Math> 5- to 10-membered heteroaryl; wherein <com:Math><semantics>Rc<annotation encoding="application / x-tex">R_c< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; <com:Math><semantics>Rd<annotation encoding="application / x-tex">R_d< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkylene and alkenylene are optionally substitued with substituent groups selected from H, D, CN, OH, =O, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10- membered heteroaryl, -O-C<com:Sub>3-7< / com:Sub> cycloalkyl, -O-4- to 7-membered heterocyclyl, -O-C<com:Sub>6-10< / com:Sub> aryl, -O-5- to 10- membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−Cδ−10<annotation encoding="application / x-tex">-C(O)-C_{\delta-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5<annotation encoding="application / x-tex">-C(O)-5< / annotation>< / semantics>< / com:Math>- to 10-membered heteroaryl, or substitued with one or more D, up to complete deuteration.

[0007] In another aspect, the present disclosure relates to a compound of formula (I), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (|) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; or <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form <com:Math><semantics>−(CH2)pY<annotation encoding="application / x-tex">-(CH_2)_pY< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Y(CH2)p<annotation encoding="application / x-tex">-Y(CH_2)_p< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−Y(CH2)pZ<annotation encoding="application / x-tex">-Y(CH_2)_pZ< / annotation>< / semantics>< / com:Math> group; wherein p is 1, 2, 3, 4 or 5; Y is selected from O, S, NH or chemical bond; Z is selected from O, S, NH or chemical bond; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is selected from <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R3′)−C(O)−<annotation encoding="application / x-tex">-N(R_3')-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−<annotation encoding="application / x-tex">-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S−<annotation encoding="application / x-tex">-S-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R″)−<annotation encoding="application / x-tex">-N(R'')-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C1−4<annotation encoding="application / x-tex">-C_{1-4}< / annotation>< / semantics>< / com:Math> alkylene- or <com:Math><semantics>−C2−4<annotation encoding="application / x-tex">-C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene-; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; R'' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-3- to 10-membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10- CA membered heteroaryl; or, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0008] In another aspect, the present disclosure provides methods for the preparation of compounds of the present disclosure.

[0009] In another aspect, the present disclosure provides a pharmaceutical composition, which comprises a compound disclosed herein and pharmaceutically acceptable excipient (s). In a specific embodiment, the compound disclosed herein is provided in a therapeutically effective amount. In a specific embodiment, the compound disclosed herein is provided in a prophylactically effective amount. In another aspect, the pharmaceutical composition of the present disclosure is used in combination with immune checkpoint inhibitor such as PD-1, PD-L1, CTLA-4 antibodies, etc.

[0010] In another aspect, the present disclosure provides the use of a compound of the present disclosure or a pharmaceutical composition of the present disclosure in the manufacture of a medicament for the treatment and / or prevention of EED- and / or PRC2-mediated diseases. In another aspect, the present disclosure provides the use of the compound of the present disclosure or the pharmaceutical composition of the present disclosure in the manufacture of a medicament for the treatment and / or prevention of immunodeficiency diseases and autoimmune diseases, etc.

[0011] In another aspect, the present disclosure provides a method of treating and / or preventing EED- and / or PRC2-mediated diseases in a subject, comprising administering to the subject a compound of the present disclosure or a pharmaceutical composition thereof.

[0012] In another aspect, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment and / or prevention of EED- and / or PRC2-mediated diseases.

[0013] In another aspect, the EED- and / or PRC2-mediated disease is a tumor-related disease, an immunodeficiency disease or an autoimmune disease; alternatively, the tumor-related disease is selected from diffuse large B-cell lymphoma, follicular lymphoma, other lymphomas, leukemia, multiple myeloma, mesothelioma, gastric cancer, malignant rhabdomyoma, liver cancer, prostate cancer, breast cancer, bile duct and gallbladder cancer, bladder cancer, brain tumors (including neuroblastoma, schwannoma, glioma, glioblastoma and astrocytoma), cervical cancer, colon cancer, melanoma, endometrial cancer, esophageal cancer, head and neck cancer, lung cancer, nasopharyngeal cancer, ovarian cancer, pancreatic cancer, renal cell cancer, rectal cancer, thyroid cancer, parathyroid tumor, uterine tumor and soft tissue sarcoma; the immunodeficiency disease or autoimmune disease includes, but is not limited to, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, aplastic anemia due to autoimmunity and rejection reaction due to organ transplantation, etc.

[0014] In another aspect, the present disclosure provides the use of the compound of the present disclosure or the pharmaceutical composition thereof in the manufacture of a medicament for tumor immunization.

[0015] In another aspect, the present disclosure provides a method for tumor immunization in a subject, comprising administering to the subject a compound of the present disclosure or a pharmaceutical composition thereof.

[0016] In another aspect, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in tumor immunization.

[0017] In another aspect, the present disclosure provides a drug combination comprising a compound of the present disclosure or a pharmaceutical composition thereof, and an immune checkpoint inhibitor.

[0018] Other objects and advantages of the present disclosure will be apparent to those skilled in the art from the detailed description, examples and claims that follow. Definitions Chemical definitions

[0019] The definitions of specific functional groups and chemical terms are described in more detail below.

[0020] When a range of values is listed, it is intended to encompass each value and sub-range within the range. For example, "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl" is intended to encompass <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−2<annotation encoding="application / x-tex">C_{1-2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>6<annotation encoding="application / x-tex">_{6}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2−5<annotation encoding="application / x-tex">C_{2-5}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2−3<annotation encoding="application / x-tex">C_{2-3}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C3−5<annotation encoding="application / x-tex">C_{3-5}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C4−6<annotation encoding="application / x-tex">C_{4-6}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C4−5<annotation encoding="application / x-tex">C_{4-5}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>C5−6<annotation encoding="application / x-tex">C_{5-6}< / annotation>< / semantics>< / com:Math> alkyl.

[0021] "C<com:Sub>1-6< / com:Sub> alkyl" refers to a linear or branched, saturated hydrocarbon group having 1 to 6 carbon atoms, and is also referred to herein as "lower alkyl". In some embodiments, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl is alternative. Examples of alkyl include, but are not limited to, methyl (<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>), ethyl (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>), n-propyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), iso-propyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), n-butyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), t- butyl (C<com:Sub>4< / com:Sub>), sec-butyl (C<com:Sub>4< / com:Sub>), iso-butyl (C<com:Sub>4< / com:Sub>), n-pentyl (C<com:Sub>5< / com:Sub>), 3-pentyl (C<com:Sub>5< / com:Sub>), pentyl (C<com:Sub>5< / com:Sub>), neo-pentyl (C<com:Sub>5< / com:Sub>), 3-methyl- 2-butyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>), t-pentyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>) and n-hexyl (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>). Regardless of whether or not the alkyl group is modified with "substituted", each alkyl group is independently optionally substituted, for example, with <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$\bf 1$ to <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$\bf 5$ substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0022] "C<com:Sub>2-6< / com:Sub> alkenyl" refers to a linear or branched, hydrocarbon group having 2-6 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). One or more carbon-carbon double bonds can be internal (e.g., in 2-butenyl) or terminal (e.g., in 1-butenyl). In some embodiments, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenyl is alternative. Examples of alkenyl include, but are not limited to, vinyl <com:Math><semantics>(C2)<annotation encoding="application / x-tex">(C_2)< / annotation>< / semantics>< / com:Math>, 1-propenyl <com:Math><semantics>(C3)<annotation encoding="application / x-tex">(C_3)< / annotation>< / semantics>< / com:Math>, 2- propenyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), 1-butenyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), 2-butenyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), butadienyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), pentenyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>), pentadienyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>), hexenyl (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>), etc. Regardless of whether or not the alkenyl group is modified with "substituted", each alkenyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0023] "C<com:Sub>2-6< / com:Sub> alkynyl" refers to a linear or branched, hydrocarbon group having 2-6 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2 or 3 carbon-carbon triple bonds) and optionally one or more carbon- carbon double bonds (e.g., 1, 2 or 3 carbon-carbon double bonds). In some embodiments, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkynyl is alternative. In some embodiments, alkynyl does not contain any double bond. One or more carbon-carbon triple bonds can be internal (e.g., in 2-butynyl) or terminal (e.g., in 1-butynyl). Examples of alkynyl include, but are not limited to, ethynyl (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>), 1-propynyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), 2-propynyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), 1-butynyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), 2-butynyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), pentynyl (C<com:Sub>5< / com:Sub>), hexynyl (C<com:Sub>6< / com:Sub>), etc. Regardless of whether or not the alkynyl group is modified with "substituted", each alkynyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0024] "-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-, -<com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkenylene- or -<com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkynylene-" refers to a divalent group of "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> 6 alkenyl or C<com:Sub>2-6< / com:Sub> alkynyl" as defined above.

[0025] "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene" refers to a divalent group formed by removing another hydrogen from a <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl group, and can be a substituted or unsubstituted alkylene group. In some embodiments, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkylene groups are particularly alternative. The unsubstituted alkylene groups include, but are not limited to, methylene (- <com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-), ethylene (<com:Math><semantics>−CH2CH2<annotation encoding="application / x-tex">-CH_2CH_2< / annotation>< / semantics>< / com:Math>-), propylene (<com:Math><semantics>−CH2CH2CH2<annotation encoding="application / x-tex">-CH_2CH_2CH_2< / annotation>< / semantics>< / com:Math>-), butylene (<com:Math><semantics>−CH2CH2CH2CH2<annotation encoding="application / x-tex">-CH_2CH_2CH_2CH_2< / annotation>< / semantics>< / com:Math>-), pentylene (<com:Math><semantics>−CH2CH2<annotation encoding="application / x-tex">-CH_2CH_2< / annotation>< / semantics>< / com:Math>-) CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-), hexylene (-CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-), etc. Exemplary substituted alkylene groups, e.g., alkylene groups substituted with one or more alkyl (methyl) groups, include, but are not limited to, substituted methylene (-CH(CH<com:Sub>3< / com:Sub>)-, -C(CH<com:Sub>3< / com:Sub>)<com:Sub>2< / com:Sub>-), substituted ethylene (-CH(CH<com:Sub>3< / com:Sub>)CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH(CH<com:Sub>3< / com:Sub>)-, - <com:Math><semantics>C(CH3)2CH2−<annotation encoding="application / x-tex">C(CH_3)_2CH_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2C(CH3)2−<annotation encoding="application / x-tex">-CH_2C(CH_3)_2-< / annotation>< / semantics>< / com:Math>), substituted propylene <com:Math><semantics>(−CH(CH3)CH2CH2−<annotation encoding="application / x-tex">(-CH(CH_3)CH_2CH_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2CH(CH3)CH2−<annotation encoding="application / x-tex">-CH_2CH(CH_3)CH_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>CH2CH2CH(CH3)−<annotation encoding="application / x-tex">CH_2CH_2CH(CH_3)_-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(CH3)2CH2CH2−<annotation encoding="application / x-tex">-C(CH_3)_2CH_2CH_2_-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2C(CH3)2CH2−<annotation encoding="application / x-tex">-CH_2C(CH_3)_2CH_2_-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2CH2C(CH3)2−<annotation encoding="application / x-tex">-CH_2CH_2C(CH_3)_2_-< / annotation>< / semantics>< / com:Math>), etc.

[0026] "<com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkenylene" refers to a divalent group formed by removing another hydrogen from a <com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkenyl group, and may be a substituted or unsubstituted alkenylene group. In some embodiments, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene groups are particularly alternative. Exemplary unsubstituted alkenylene groups include, but are not limited to, vinylene (-CH=CH-) and propylene (e.g., -CH=CHCH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>-CH=CH-). Exemplary substituted alkenylene groups, e.g., alkenylene groups substituted with one or more alkyl (methyl) groups, include, but are not limited to, substituted ethylene (<com:Math><semantics>−C(CH3)=CH−<annotation encoding="application / x-tex">-C(CH_3)=CH-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=C(CH3)−<annotation encoding="application / x-tex">-CH=C(CH_3)-< / annotation>< / semantics>< / com:Math>), substituted propenylene (- <com:Math><semantics>C(CH3)=CHCH2−<annotation encoding="application / x-tex">C(CH_3)=CHCH_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=C(CH3)CH2−<annotation encoding="application / x-tex">-CH=C(CH_3)CH_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=CHCH(CH3)−<annotation encoding="application / x-tex">-CH=CHCH(CH_3)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=CHC(CH3)2−<annotation encoding="application / x-tex">-CH=CHC(CH_3)_2-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH(CH3)−CH=CH−<annotation encoding="application / x-tex">-CH(CH_3)-CH=CH-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(CH3)2<annotation encoding="application / x-tex">C(CH_3)_2< / annotation>< / semantics>< / com:Math>-CH=CH-, -CH<com:Sub>2< / com:Sub>-C(CH<com:Sub>3< / com:Sub>)=CH-, -CH<com:Sub>2< / com:Sub>-CH=C(CH<com:Sub>3< / com:Sub>)-), etc.

[0027] "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxyl" refers to a -OR group, wherein R is substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkoxyl is alternative. Specifically, alkoxyl includes, but is not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, t-butoxy, sec-butoxy, n-pentyloxy, n-hexyloxy and 1,2-dimethylbutoxy.

[0028] "Halo" or "halogen" refers to fluoro (F), chloro (Cl), bromo (Br) and iodo (1). In some embodiments, the halo group is F, Cl or Br. In some embodiments, the halo group is F or Cl. In some embodiments, the halo group is F.

[0029] Therefore, "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl" and "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxyl" refer to the above "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl" and "<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxyl" substituted with one or more halo groups. In some embodiments, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> haloalkyl is alternative, and <com:Math><semantics>C1−2<annotation encoding="application / x-tex">C_{1-2}< / annotation>< / semantics>< / com:Math> haloalkyl is yet alternative. In some embodiments, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> haloalkoxyl is alternative, and <com:Math><semantics>C1−2<annotation encoding="application / x-tex">C_{1-2}< / annotation>< / semantics>< / com:Math> haloalkoxyl is yet alternative. Examples of haloalkyl include, but are not limited to, -CF<com:Sub>3< / com:Sub>, -CH<com:Sub>2< / com:Sub>F, -CHF<com:Sub>2< / com:Sub>, -CHFCH<com:Sub>2< / com:Sub>F, -CH<com:Sub>2< / com:Sub>CHF<com:Sub>2< / com:Sub>, -CF<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>, -CCl<com:Sub>3< / com:Sub>, -CH<com:Sub>2< / com:Sub>Cl, -CHCl<com:Sub>2< / com:Sub>, 2,2,2-trifluoro-1,1-dimethyl-ethyl, etc. Examples of haloalkoxyl include, but are not limited to, -OCH<com:Sub>2< / com:Sub>F, -OCHF<com:Sub>2< / com:Sub>, -OCF<com:Sub>3< / com:Sub>, etc.

[0030] "C<com:Sub>3-10< / com:Sub> cycloalkyl" refers to a non-aromatic cyclic hydrocarbon group having 3-10 ring carbon atoms and zero heteroatoms. In some embodiments, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl is alternative, <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl is alternative, and <com:Math><semantics>C5−6<annotation encoding="application / x-tex">C_{5-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and <com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl are yet alternative. Cycloalkyl also includes a ring system in which the above cycloalkyl ring is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the cycloalkyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the cycloalkyl system. Examples of cycloalkyl include, but are not limited to, cyclopropyl (C<com:Sub>3< / com:Sub>), cyclopropenyl (<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>), cyclobutyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), cyclobutenyl (<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>), cyclopentyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>), cyclopentenyl (<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math>), cyclohexyl (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>), cyclohexenyl (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>), cyclohexadienyl (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>), cycloheptyl (<com:Math><semantics>C7<annotation encoding="application / x-tex">C_7< / annotation>< / semantics>< / com:Math>), cycloheptenyl (<com:Math><semantics>C7<annotation encoding="application / x-tex">C_7< / annotation>< / semantics>< / com:Math>), cycloheptadienyl (<com:Math><semantics>C7<annotation encoding="application / x-tex">C_7< / annotation>< / semantics>< / com:Math>), cycloheptatrienyl (<com:Math><semantics>C7<annotation encoding="application / x-tex">C_7< / annotation>< / semantics>< / com:Math>), cyclooctyl (<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>), cyclooctenyl (<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>), bicyclo[2.2.1]heptyl (<com:Math><semantics>C7<annotation encoding="application / x-tex">C_7< / annotation>< / semantics>< / com:Math>), bicyclo[2.2.2]octyl (<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>), cyclononyl (<com:Math><semantics>C9<annotation encoding="application / x-tex">C_9< / annotation>< / semantics>< / com:Math>), cyclononenyl (<com:Math><semantics>C9<annotation encoding="application / x-tex">C_9< / annotation>< / semantics>< / com:Math>), cyclodecyl (<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>), cyclodecenyl (<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>), octahydro-1H-indenyl (<com:Math><semantics>C9<annotation encoding="application / x-tex">C_9< / annotation>< / semantics>< / com:Math>), decahydronaphthyl (<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>), spiro[4.5]decyl (<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>), etc. Regardless of whether or not the cycloalkyl group is modified with "substituted", each cycloalkyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0031] "3- to 10-membered heterocycly!" refers to a radical of a 3- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. In some embodiments, 4- to 7-membered heterocyclyl is alternative, and it is a 4- to 7-membered non-aromatic ring system having ring carbon atoms and 1-3 ring heteroatoms. In some embodiments, 3- to 6-membered heterocyclyl is alternative, and it is a 3- to 6-membered non-aromatic ring system having ring carbon atoms and 1-3 ring heteroatoms. 5- to 6-membered heterocyclyl is yet alternative, and it is a 5- to 6-membered non- aromatic ring system having ring carbon atoms and 1-3 ring heteroatoms. "Heterocycly!" also includes ring systems wherein the heterocyclyl, as defined above, is fused with one or more cycloalkyl, aryl or heteroaryl groups wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continues to designate the number of ring members in the heterocyclyl ring system. Regardless of whether or not the heterocyclyl group is modified with "substituted", each heterocyclyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0032] Exemplary 3-membered heterocyclyl groups containing one heteroatom include, without limitation, azirdinyl, oxiranyl, thiorenyl. Exemplary 4-membered heterocyclyl groups containing one heteroatom include, without limitation, azetidinyl, oxetanyl and thietanyl. Exemplary 5-membered heterocyclyl groups containing one heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, without limitation, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, dioxanyl. Exemplary 6-membered heterocyclyl groups containing three heteroatoms include, without limitation, triazinanyl. Exemplary 7- membered heterocyclyl groups containing one heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary 5-membered heterocyclyl groups fused to a C<com:Sub>6< / com:Sub> aryl ring (also referred to herein as a 5,6-bicyclic heterocyclyl) include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like. Exemplary 6-membered heterocyclyl groups fused to a C<com:Sub>6< / com:Sub> aryl ring (also referred to herein as a 6,6-bicyclic heterocyclyl) include, without limitation, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0033] "C<com:Sub>6-14< / com:Sub> aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms. In some embodiments, an aryl group has six ring carbon atoms ("C<com:Sub>6< / com:Sub> aryl"; e.g., phenyl). In some embodiments, an aryl group has ten ring carbon atoms ("C<com:Sub>10< / com:Sub> aryl"; e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms ("<com:Math><semantics>C14<annotation encoding="application / x-tex">C_{14}< / annotation>< / semantics>< / com:Math> aryl"; e.g., anthracyl). In some embodiments, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl is alternative, and <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> aryl is yet alternative. "Aryl" also includes ring systems wherein the aryl ring, as defined above, is fused with one or more cycloalkyl or heterocyclyl groups wherein the point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continues to designate the number of carbon atoms in the aryllring system. Regardless of whether or not the aryll group is modified with "substituted", each aryl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0034] "5- to 10-membered heteroary?" refers to a radical of a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 pi electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur. In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl bicyclic ring systems can include one or more heteroatoms in one or both rings. "Heteroaryl" also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more cycloalkyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of carbon atoms continues to designate the number of carbon atoms in the heteroaryl ring system. In some embodiments, 5- to 6-membered heteroaryl is alternative, and it is a 5- to 6-membered monocyclic or bicyclic 4n+2 aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms. Regardless of whether or not the heteroaryl group is modified with "substituted", each heteroaryl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent. Appropriate substituents are defined as follows.

[0035] Exemplary 5-membered heteroaryl groups containing one heteroatom include, without limitation, pyrrolyl, furanyl and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, without limitation, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, without limitation, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, without limitation, , oxepinyl, and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0036] Exemplary substituents on carbon atoms include, but are not limited to, halo, -CN, -NO<com:Sub>2< / com:Sub>, -N<com:Sub>3< / com:Sub>, -SO<com:Sub>2< / com:Sub>H, <com:Math><semantics>−SO3H<annotation encoding="application / x-tex">-SO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OH<annotation encoding="application / x-tex">-OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−ORaa<annotation encoding="application / x-tex">-OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−ON(Rbb)2<annotation encoding="application / x-tex">-ON(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Rbb)2<annotation encoding="application / x-tex">-N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Rbb)3<annotation encoding="application / x-tex">-N(R^{bb})_3< / annotation>< / semantics>< / com:Math><com:Sup>+< / com:Sup>X<com:Sup>-< / com:Sup>, <com:Math><semantics>−N(ORcc)Rbb<annotation encoding="application / x-tex">-N(OR^{cc})R^{bb}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SH<annotation encoding="application / x-tex">-SH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SRaa<annotation encoding="application / x-tex">-SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SSRcc<annotation encoding="application / x-tex">-SSR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)Raa<annotation encoding="application / x-tex">-C(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2H<annotation encoding="application / x-tex">-CO_2H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO3H<annotation encoding="application / x-tex">-CO_3H< / annotation>< / semantics>< / com:Math> CHO, <com:Math><semantics>−C(ORcc)2<annotation encoding="application / x-tex">-C(OR^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Raa<annotation encoding="application / x-tex">-CO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)Raa<annotation encoding="application / x-tex">-OC(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OCO2Raa<annotation encoding="application / x-tex">-OCO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)N(Rbb)2<annotation encoding="application / x-tex">-C(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)N(Rbb)2<annotation encoding="application / x-tex">-OC(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbC(=O)Raa<annotation encoding="application / x-tex">-NR^{bb}C(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)N(Rbb)2<annotation encoding="application / x-tex">-C(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)N(Rbb)2<annotation encoding="application / x-tex">-OC(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)N(Rbb)2<annotation encoding="application / x-tex">-OC(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)N(Rbb)2<annotation encoding="application / x-tex">-OC(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NRbbCO2Raa<annotation encoding="application / x-tex">NR^{bb}CO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbC(=O)N(Rbb)2<annotation encoding="application / x-tex">-NR^{bb}C(=O)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRbb)Raa<annotation encoding="application / x-tex">-C(=NR^{bb})R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRbb)ORaa<annotation encoding="application / x-tex">-C(=NR^{bb})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)Raa<annotation encoding="application / x-tex">-OC(=NR^{bb})R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)ORaa<annotation encoding="application / x-tex">-OC(=NR^{bb})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)ORaa<annotation encoding="application / x-tex">-OC(=NR^{bb})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)ORaa<annotation encoding="application / x-tex">-OC(=NR^{bb})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)ORaa<annotation encoding="application / x-tex">-OC(=NR^{bb})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NR<annotation encoding="application / x-tex">-OC(=NR< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(=NRbb)N(Rbb)2<annotation encoding="application / x-tex">C(=NR^{bb})N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRbb)N(Rbb)2<annotation encoding="application / x-tex">-OC(=NR^{bb})N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbC(=NRbb)N(Rbb)2<annotation encoding="application / x-tex">-NR^{bb}C(=NR^{bb})N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)NRbbSO2Raa<annotation encoding="application / x-tex">-C(=O)NR^{bb}SO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbSO2Raa<annotation encoding="application / x-tex">-NR^{bb}SO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>SO2N(Rbb)2<annotation encoding="application / x-tex">SO_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Raa<annotation encoding="application / x-tex">-SO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORaa<annotation encoding="application / x-tex">-SO_2OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSO2Raa<annotation encoding="application / x-tex">-OSO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(=O)Raa<annotation encoding="application / x-tex">-S(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OS(=O)Raa<annotation encoding="application / x-tex">-OS(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Si(Raa)3<annotation encoding="application / x-tex">-Si(R^{aa})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSi(Raa)3<annotation encoding="application / x-tex">-OSi(R^{aa})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rbb)2<annotation encoding="application / x-tex">-C(=S)N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rbb)3<annotation encoding="application / x-tex">-C(=S)N(R^{bb})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rbb)4<annotation encoding="application / x-tex">-C(=S)N(R^{bb})_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rbb)4<annotation encoding="application / x-tex">-C(=S)N(R^{bb})_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C<annotation encoding="application / x-tex">-C< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(=O)SRaa<annotation encoding="application / x-tex">C(=O)SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRaa<annotation encoding="application / x-tex">-C(=S)SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SC(=S)SRaa<annotation encoding="application / x-tex">-SC(=S)SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SC(=O)SRaa<annotation encoding="application / x-tex">-SC(=O)SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)SRaa<annotation encoding="application / x-tex">-OC(=O)SR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SC(=O)ORaa<annotation encoding="application / x-tex">-SC(=O)OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SC(=O)Raa<annotation encoding="application / x-tex">-SC(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2Raa<annotation encoding="application / x-tex">-P(=O)_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)2Raa<annotation encoding="application / x-tex">-OP(=O)_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(Raa)2<annotation encoding="application / x-tex">-P(=O)(R^{aa})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)(Raa)2<annotation encoding="application / x-tex">-OP(=O)(R^{aa})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)(ORcc)2<annotation encoding="application / x-tex">-OP(=O)(OR^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2N(Rbb)2<annotation encoding="application / x-tex">-P(=O)_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)2N(Rbb)2<annotation encoding="application / x-tex">-OP(=O)_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)2N(Rbb)2<annotation encoding="application / x-tex">-OP(=O)_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)2N(Rbb)2<annotation encoding="application / x-tex">-OP(=O)_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)2N(Rbb)2<annotation encoding="application / x-tex">-OP(=O)_2N(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$-OP(=O)_2N(R^{bb})_$ <com:Math><semantics>P(=O)(NRbb)2<annotation encoding="application / x-tex">P(=O)(NR^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)(NRbb)2<annotation encoding="application / x-tex">-OP(=O)(NR^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbP(=O)(ORcc)2<annotation encoding="application / x-tex">-NR^{bb}P(=O)(OR^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRbbP(=O)(NRbb)2<annotation encoding="application / x-tex">-NR^{bb}P(=O)(NR^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(Rcc)2<annotation encoding="application / x-tex">-P(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(Rcc)3<annotation encoding="application / x-tex">-P(R^{cc})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(Rcc)2<annotation encoding="application / x-tex">-OP(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(Rcc)3<annotation encoding="application / x-tex">-P(R^{cc})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(Rcc)2<annotation encoding="application / x-tex">-OP(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(Rcc)3<annotation encoding="application / x-tex">-P(R^{cc})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(Rcc)3<annotation encoding="application / x-tex">-OP(R^{cc})_3< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>-OP(R^{ <com:Math><semantics>OP(Rcc)3<annotation encoding="application / x-tex">OP(R^{cc})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−B(Raa)2<annotation encoding="application / x-tex">-B(R^{aa})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−B(ORcc)2<annotation encoding="application / x-tex">-B(OR^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−BRaa(ORcc)<annotation encoding="application / x-tex">-BR^{aa}(OR^{cc})< / annotation>< / semantics>< / com:Math>, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>dd< / com:Sup> groups;

[0037] or two geminal hydrogens on a carbon atom are replaced with the group <com:Math><semantics>=0<annotation encoding="application / x-tex">=0< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=S<annotation encoding="application / x-tex">=S< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=NN(Rbb)2<annotation encoding="application / x-tex">=NN(R^{bb})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=NNRbbC(=O)Raa<annotation encoding="application / x-tex">=NNR^{bb}C(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=NNRbbC(=O)ORaa<annotation encoding="application / x-tex">=NNR^{bb}C(=O)OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=NNRbbS(=O)2Raa<annotation encoding="application / x-tex">=NNR^{bb}S(=O)_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=NRbb<annotation encoding="application / x-tex">=NR^{bb}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>=NORcc<annotation encoding="application / x-tex">=NOR^{cc}< / annotation>< / semantics>< / com:Math>;

[0038] each Raa is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two Raa groups are bound to form heterocyclyl or heteroaryl ring, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>dd< / com:Sup> groups;

[0039] each <com:Math><semantics>Rbb<annotation encoding="application / x-tex">R^{bb}< / annotation>< / semantics>< / com:Math> is independently selected from: hydrogen, -OH, -OR<com:Sup>aa< / com:Sup>, -N(R<com:Sup>cc< / com:Sup>)<com:Sub>2< / com:Sub>, -CN, -C(=O)R<com:Sup>aa< / com:Sup>, - <com:Math><semantics>C(=O)N(Rcc)2<annotation encoding="application / x-tex">C(=O)N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Raa<annotation encoding="application / x-tex">-CO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Raa<annotation encoding="application / x-tex">-SO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)ORaa<annotation encoding="application / x-tex">-C(=NR^{cc})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)N(Rcc)2<annotation encoding="application / x-tex">-C(=NR^{cc})N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2N(Rcc)2<annotation encoding="application / x-tex">-SO_2N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Rcc<annotation encoding="application / x-tex">-SO_2R^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2<annotation encoding="application / x-tex">-SO_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>SORaa<annotation encoding="application / x-tex">SOR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rcc)2<annotation encoding="application / x-tex">-C(=S)N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRcc<annotation encoding="application / x-tex">-C(=O)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2Raa<annotation encoding="application / x-tex">-P(=O)_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(Raa)2<annotation encoding="application / x-tex">-P(=O)(R^{aa})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2N(Rcc)2<annotation encoding="application / x-tex">-P(=O)_2N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(NRcc)2<annotation encoding="application / x-tex">-P(=O)(NR^{cc})_2< / annotation>< / semantics>< / com:Math>, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R<com:Sup>bb< / com:Sup> groups are bound to form heterocyclyl or heteroaryl ring, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>dd< / com:Sup> groups;

[0040] each R<com:Sup>cc< / com:Sup> is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R<com:Sup>cc< / com:Sup> groups are bound to form heterocyclyl or heteroaryl ring, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>dd< / com:Sup> groups;

[0041] each <com:Math><semantics>Rdd<annotation encoding="application / x-tex">R^{dd}< / annotation>< / semantics>< / com:Math> is independently selected from: halo, -CN, -NO<com:Sub>2< / com:Sub>, -N<com:Sub>3< / com:Sub>, -SO<com:Sub>2< / com:Sub>H, -SO<com:Sub>3< / com:Sub>H, -OH, -OR<com:Sup>ee< / com:Sup>, - <com:Math><semantics>ON(Rff)2<annotation encoding="application / x-tex">ON(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Rff)2<annotation encoding="application / x-tex">-N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Rff)3+X−<annotation encoding="application / x-tex">-N(R^{ff})_3 + X^-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(ORee)Rff<annotation encoding="application / x-tex">-N(OR^{ee})R^{ff}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SH<annotation encoding="application / x-tex">-SH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SRee<annotation encoding="application / x-tex">-SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SSRee<annotation encoding="application / x-tex">-SSR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)Ree<annotation encoding="application / x-tex">-C(=O)R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2H<annotation encoding="application / x-tex">-CO_2H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Ree<annotation encoding="application / x-tex">-CO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)Ree<annotation encoding="application / x-tex">-OC(=O)R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2H<annotation encoding="application / x-tex">-CO_2H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Ree<annotation encoding="application / x-tex">-CO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)Ree<annotation encoding="application / x-tex">-OC(=O)R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Ree<annotation encoding="application / x-tex">-CO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OCO2Ree<annotation encoding="application / x-tex">OCO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)N(Rff)2<annotation encoding="application / x-tex">-C(=O)N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)N(Rff)2<annotation encoding="application / x-tex">-OC(=O)N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRffC(=O)Ree<annotation encoding="application / x-tex">-NR^{ff}C(=O)R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRffCO2Ree<annotation encoding="application / x-tex">-NR^{ff}CO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRffC(=O)N(Rff)2<annotation encoding="application / x-tex">-NR^{ff}C(=O)N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRff)ORee<annotation encoding="application / x-tex">-C(=NR^{ff})OR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRff)Ree<annotation encoding="application / x-tex">-OC(=NR^{ff})R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRff)ORee<annotation encoding="application / x-tex">-OC(=NR^{ff})OR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRff)N(Rff)2<annotation encoding="application / x-tex">-C(=NR^{ff})N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NRff)N(Rff)2<annotation encoding="application / x-tex">-OC(=NR^{ff})N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRffC(=NRff)N(Rff)2<annotation encoding="application / x-tex">-NR^{ff}C(=NR^{ff})N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRffSO2Ree<annotation encoding="application / x-tex">-NR^{ff}SO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2N(Rff)2<annotation encoding="application / x-tex">-SO_2N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Ree<annotation encoding="application / x-tex">-SO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORee<annotation encoding="application / x-tex">-SO_2OR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSO2Ree<annotation encoding="application / x-tex">-OSO_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(=O)Ree<annotation encoding="application / x-tex">-S(=O)R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Si(Ree)3<annotation encoding="application / x-tex">-Si(R^{ee})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSi(Ree)3<annotation encoding="application / x-tex">-OSi(R^{ee})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rff)2<annotation encoding="application / x-tex">-C(=S)N(R^{ff})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRee<annotation encoding="application / x-tex">-C(=O)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRee<annotation encoding="application / x-tex">-C(=O)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRee<annotation encoding="application / x-tex">-C(=O)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRee<annotation encoding="application / x-tex">-C(=O)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRee<annotation encoding="application / x-tex">-C(=O)SR^{ee}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(=S)SRee<annotation encoding="application / x-tex">C(=S)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SC(=S)SRee<annotation encoding="application / x-tex">-SC(=S)SR^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2Ree<annotation encoding="application / x-tex">-P(=O)_2R^{ee}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(Ree)2<annotation encoding="application / x-tex">-P(=O)(R^{ee})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)(Ree)2<annotation encoding="application / x-tex">-OP(=O)(R^{ee})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(=O)(ORee)2<annotation encoding="application / x-tex">-OP(=O)(OR^{ee})_2< / annotation>< / semantics>< / com:Math>, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>99< / com:Sup> groups, or two geminal <com:Math><semantics>Rdd<annotation encoding="application / x-tex">R^{dd}< / annotation>< / semantics>< / com:Math> substituents can be bound to form =O or =S;

[0042] each Ree is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, aryl, heterocyclyl and heteroaryl, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 Rgg groups;

[0043] each Rff is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two Rff groups are bound to form heterocyclyl or heteroaryl ring, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>99< / com:Sup> groups;

[0044] each <com:Math><semantics>Rgg<annotation encoding="application / x-tex">R^{gg}< / annotation>< / semantics>< / com:Math> is independently: halo, -CN, -NO<com:Sub>2< / com:Sub>, -N<com:Sub>3< / com:Sub>, -SO<com:Sub>2< / com:Sub>H, -SO<com:Sub>3< / com:Sub>H, -OH, -OC<com:Sub>1-6< / com:Sub> alkyl, -ON(C<com:Sub>1-6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−N(C1−6 alkyl)2<annotation encoding="application / x-tex">-N(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−6 alkyl)3+X2<annotation encoding="application / x-tex">-N(C_{1-6} \text{ alkyl})_3 + X^2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH(C1−6 alkyl)2+X2<annotation encoding="application / x-tex">-NH(C_{1-6} \text{ alkyl})_2 + X^2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2(C1−6 alkyl)+X2<annotation encoding="application / x-tex">-NH_2(C_{1-6} \text{ alkyl}) + X^2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH3+X2<annotation encoding="application / x-tex">-NH_3 + X^2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(OC1−6 alkyl)(C1−6 alkyl)2+X2<annotation encoding="application / x-tex">-N(OC_{1-6} \text{ alkyl})(C_{1-6} \text{ alkyl})_2 + X^2< / annotation>< / semantics>< / com:Math> alkyl), -N(OH)(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl), -NH(OH), -SH, -SC<com:Sub>1-6< / com:Sub> alkyl, -SS(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl), -C(=O)(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl), -CO<com:Sub>2< / com:Sub>H, -CO<com:Sub>2< / com:Sub>(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> <com:Sub>6< / com:Sub> alkyl), <com:Math><semantics>−OC(=O)(C1−6 alkyl)<annotation encoding="application / x-tex">-OC(=O)(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OCO2(C1−6 alkyl)<annotation encoding="application / x-tex">-OCO_2(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)NH2<annotation encoding="application / x-tex">-C(=O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)N(C1−6 alkyl)2<annotation encoding="application / x-tex">-C(=O)N(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=O)NH(C1−6 alkyl)<annotation encoding="application / x-tex">-OC(=O)NH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC(=O)(C1−6 alkyl),−N(C1−6 alkyl)C(=O)(C1−6 alkyl),−NHCO2(C1−6 alkyl),−NHC(=O)N(C1−6 alkyl)2,−<annotation encoding="application / x-tex">-NHC(=O)(C_{1-6} \text{ alkyl}), -N(C_{1-6} \text{ alkyl})C(=O)(C_{1-6} \text{ alkyl}), -NHCO_2(C_{1-6} \text{ alkyl}), -NHC(=O)N(C_{1-6} \text{ alkyl})_2, -< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NHC(=O)NH(C1−6|a|kyl),−NHC(=O)NH2,−C(=NH)O(C1−6|a|kyl),−OC(=NH)(C1−6|a|kyl),−OC(=NH)OC1−6<annotation encoding="application / x-tex">NHC(=O)NH(C_{1-6} | a|kyl), -NHC(=O)NH_2, -C(=NH)O(C_{1-6} | a|kyl), -OC(=NH)(C_{1-6} | a|kyl), -OC(=NH)OC_{1-6}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>a|ky|<annotation encoding="application / x-tex">a|ky|< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NH)N(C1−6a|ky|)2<annotation encoding="application / x-tex">-C(=NH)N(C_{1-6} \ a|ky|)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NH)NH(C1−6a|ky|)<annotation encoding="application / x-tex">-C(=NH)NH(C_{1-6} \ a|ky|)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NH)NH2<annotation encoding="application / x-tex">-C(=NH)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(=NH)N(C1−6a|ky|)2<annotation encoding="application / x-tex">-OC(=NH)N(C_{1-6} \ a|ky|)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>OC(NH)NH(C1−6 alkyl)<annotation encoding="application / x-tex">OC(NH)NH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(NH)NH2<annotation encoding="application / x-tex">-OC(NH)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC(NH)N(C1−6 alkyl)2<annotation encoding="application / x-tex">-NHC(NH)N(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC(=NH)NH2<annotation encoding="application / x-tex">-NHC(=NH)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHSO2(C1−6 alkyl)<annotation encoding="application / x-tex">-NHSO_2(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>SO2N(C1−6 alkyl)2<annotation encoding="application / x-tex">SO_2N(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2NH(C1−6 alkyl)<annotation encoding="application / x-tex">-SO_2NH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2NH2<annotation encoding="application / x-tex">-SO_2NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2C1−6 alkyl<annotation encoding="application / x-tex">-SO_2C_{1-6} \text{ alkyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2OC1−6 alkyl<annotation encoding="application / x-tex">-SO_2OC_{1-6} \text{ alkyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSO2C1−6 alkyl<annotation encoding="application / x-tex">-OSO_2C_{1-6} \text{ alkyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SOC1−6<annotation encoding="application / x-tex">-SOC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−Si(C1−6 alkyl)3<annotation encoding="application / x-tex">-Si(C_{1-6} \text{ alkyl})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OSi(C1−6 alkyl)3<annotation encoding="application / x-tex">-OSi(C_{1-6} \text{ alkyl})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(C1−6 alkyl)2<annotation encoding="application / x-tex">-C(=S)N(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(=S)NH(C1−6 alkyl)<annotation encoding="application / x-tex">C(=S)NH(C_{1-6} \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(=S)NH2<annotation encoding="application / x-tex">C(=S)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)S(C1−6 alkyl)2<annotation encoding="application / x-tex">-C(=O)S(C_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>−C(=S)SC1−6<annotation encoding="application / x-tex">-C(=S)SC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−SC(=S)SC1−6<annotation encoding="application / x-tex">-SC(=S)SC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−P(=O)2(C1−6<annotation encoding="application / x-tex">-P(=O)_2(C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>−P(=O)(C1−6<annotation encoding="application / x-tex">-P(=O)(C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−OP(=O)(C1−6<annotation encoding="application / x-tex">-OP(=O)(C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−OP(=O)(C1−6<annotation encoding="application / x-tex">-OP(=O)(C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−OP(=O)(C1−6<annotation encoding="application / x-tex">-OP(=O)(C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−OP(=O)(C1−6<annotation encoding="application / x-tex">-OP(=O)(C_{1-6}< / annotation>< / semantics>< / com:Math> alky <com:Math><semantics>OP(=O)(OC1−6 alkyl)2<annotation encoding="application / x-tex">OP(=O)(OC_{1-6} \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−6 alkyl<annotation encoding="application / x-tex">C_{1-6} \text{ alkyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−6 haloalkyl<annotation encoding="application / x-tex">C_{1-6} \text{ haloalkyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2−C6 alkenyl<annotation encoding="application / x-tex">C_2-C_6 \text{ alkenyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2−C6 alkynyl<annotation encoding="application / x-tex">C_2-C_6 \text{ alkynyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C3−C7 carbocyclyl<annotation encoding="application / x-tex">C_3-C_7 \text{ carbocyclyl}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C6−C10 aryl<annotation encoding="application / x-tex">C_6-C_{10} \text{ aryl}< / annotation>< / semantics>< / com:Math>, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl; or two geminal R<com:Sup>gg< / com:Sup> substituents can be bound to form <com:Math><semantics>=0<annotation encoding="application / x-tex">= 0< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>=S<annotation encoding="application / x-tex">= S< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>X−<annotation encoding="application / x-tex">X^-< / annotation>< / semantics>< / com:Math> is a counter ion.

[0045] Exemplary substituents on the nitrogen atom include but are not limited to, hydrogen, -OH, -OR®, <com:Math><semantics>−N(Rcc)2<annotation encoding="application / x-tex">-N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)Raa<annotation encoding="application / x-tex">-C(=O)R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)N(Rcc)2<annotation encoding="application / x-tex">-C(=O)N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CO2Raa<annotation encoding="application / x-tex">-CO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Raa<annotation encoding="application / x-tex">-SO_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRbb)Raa<annotation encoding="application / x-tex">-C(=NR^{bb})R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)ORaa<annotation encoding="application / x-tex">-C(=NR^{cc})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)ORaa<annotation encoding="application / x-tex">-C(=NR^{cc})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)ORaa<annotation encoding="application / x-tex">-C(=NR^{cc})OR^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=NRcc)ORaa<annotation encoding="application / x-tex">-C(=NR^{cc})OR^{aa}< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>-C(=NR^{cc})OR^{ <com:Math><semantics>C(=NRcc)N(Rcc)2<annotation encoding="application / x-tex">C(=NR^{cc})N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2N(Rcc)2<annotation encoding="application / x-tex">-SO_2N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2Rcc<annotation encoding="application / x-tex">-SO_2R^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SO2ORcc<annotation encoding="application / x-tex">-SO_2OR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)N(Rcc)2<annotation encoding="application / x-tex">-C(=S)N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=O)SRcc<annotation encoding="application / x-tex">-C(=O)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=S)SRcc<annotation encoding="application / x-tex">-C(=S)SR^{cc}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(=<annotation encoding="application / x-tex">-C(=< / annotation>< / semantics>< / com:Math> <com:Math><semantics>P(=O)2Raa<annotation encoding="application / x-tex">P(=O)_2R^{aa}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(Raa)2<annotation encoding="application / x-tex">-P(=O)(R^{aa})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)2N(Rcc)2<annotation encoding="application / x-tex">-P(=O)_2N(R^{cc})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−P(=O)(NRcc)2<annotation encoding="application / x-tex">-P(=O)(NR^{cc})_2< / annotation>< / semantics>< / com:Math>, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R<com:Sup>cc< / com:Sup> groups connected to the nitrogen atom are bound to form heterocyclyl or heteroaryl ring, wherein each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted with 0, 1, 2, 3, 4 or 5 R<com:Sup>dd< / com:Sup> groups, and wherein R<com:Sup>aa< / com:Sup>, R<com:Sup>bb< / com:Sup>, R<com:Sup>cc< / com:Sup> and R<com:Sup>dd< / com:Sup> are as defined above.

[0046] The term "pharmaceutically acceptable salt" refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1-19. Pharmaceutically acceptable salts of the compounds disclosed herein include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid. Salts formed using conventional methods in the art such as ion exchange are also included. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and <com:Math><semantics>N+(C1−4alkyl)4<annotation encoding="application / x-tex">N^+(C_{1-4}alkyl)_4< / annotation>< / semantics>< / com:Math> salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.

[0047] A "subject" to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle-aged adult or senior adult)) and / or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human," "patient," and "subject" are used interchangeably herein.

[0048] "Disease", "disorder" and "condition" are used interchangeably herein.

[0049] As used herein, and unless otherwise specified, the terms "treat," "treating" and "treatment" contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or retards or slows the progression of the disease, disorder or condition ("therapeutic treatment"), and also contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition ("prophylactic treatment").

[0050] "Combination", "combined", and related terms refer to the simultaneous or sequential administration of the therapeutic agents of the present disclosure. For example, the compound disclosed herein may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms, or together in a single unit dosage form. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG. 1 shows the changes in tumor volume in the Karpas422 CDX efficacy study.

[0052] FIG. 2 shows the relative changes in the body weight of mice in the Karpas422 CDX efficacy study. DETAILED DESCRIPTION OF THE INVENTION

[0053] Compounds

[0054] As used herein, "compounds of the present disclosure" refers to compounds of formula (X) or formulas (I) to (VII) below (including subsets of each formula), or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

[0055] In one embodiment, the present disclosure relates to a compound of formula (X), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (X) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; or <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form <com:Math><semantics>−(CH2)pY<annotation encoding="application / x-tex">-(CH_2)_pY< / annotation>< / semantics>< / com:Math> -, <com:Math><semantics>−Y(CH2)p<annotation encoding="application / x-tex">-Y(CH_2)_p< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−Y(CH2)pZ<annotation encoding="application / x-tex">-Y(CH_2)_pZ< / annotation>< / semantics>< / com:Math>- group; wherein p is 1, 2, 3, 4 or 5; Y is selected from O, S, NH or chemical bond; Z is selected from O, S, NH or chemical bond; <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^{2}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is selected from <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R3′)−C(O)−<annotation encoding="application / x-tex">-N(R_3')-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−C(O)−<annotation encoding="application / x-tex">-O-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−N(R)−<annotation encoding="application / x-tex">-S(O)_q-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−O−<annotation encoding="application / x-tex">-S(O)_q-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−<annotation encoding="application / x-tex">-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S−<annotation encoding="application / x-tex">-S-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−<annotation encoding="application / x-tex">-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)−<annotation encoding="application / x-tex">-S(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R″)<annotation encoding="application / x-tex">N(R'')< / annotation>< / semantics>< / com:Math>-, -<com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkylene- or -<com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene-; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; <com:Math><semantics>R**<annotation encoding="application / x-tex">R^{**}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; q is 0, 1 or 2; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a< / com:Sub>R<com:Sub>b< / com:Sub>, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-OR<com:Sub>a< / com:Sub>, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>3-7< / com:Sub> cycloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-3- to 10-membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>5-10< / com:Sub> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-; or, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; wherein R₃ is optionally substituted by one or more substituent groups selected from H, D, halogen, CN, OH, =O, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>3-7< / com:Sub> cycloalkyl, 4- to 7-membered heterocyclyl, C<com:Sub>6-10< / com:Sub> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>−O−C3−7<annotation encoding="application / x-tex">-O-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−O−4−<annotation encoding="application / x-tex">-O-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−O−C6−10<annotation encoding="application / x-tex">-O-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−O−5−<annotation encoding="application / x-tex">-O-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−S(O)q−C3−7<annotation encoding="application / x-tex">-S(O)_q-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−S(O)q−4<annotation encoding="application / x-tex">-S(O)_q-4< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−S(O)q−C6−10<annotation encoding="application / x-tex">-S(O)_q-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−S(O)q−1<annotation encoding="application / x-tex">-S(O)_q-1< / annotation>< / semantics>< / com:Math> 5- to 10-membered heteroary; wherein <com:Math><semantics>Rc<annotation encoding="application / x-tex">R_c< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered CA heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; <com:Math><semantics>Rd<annotation encoding="application / x-tex">R_d< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkylene and alkenylene are optionally substitued with substituent groups selected from H, D, CN, OH, =O, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10- membered heteroaryl, -O-C<com:Sub>3-7< / com:Sub> cycloalkyl, -O-4- to 7-membered heterocyclyl, -O-C<com:Sub>6-10< / com:Sub> aryl, -O-5- to 10- membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5<annotation encoding="application / x-tex">-C(O)-5< / annotation>< / semantics>< / com:Math>- to 10-membered heteroaryl, or substitued with one or more D, up to complete deuteration.

[0056] X

[0057] In one embodiment, X is N; in another embodiment, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>.

[0058] In more specific embodiments, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; in another specific embodiment, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is H; in another specific embodiment, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is halogen, alternatively F; in another specific embodiment, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another specific embodiment, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0059] <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math>

[0060] In one embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>H2<annotation encoding="application / x-tex">H_2< / annotation>< / semantics>< / com:Math>; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is halogen; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0061] In one embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; in another embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>Hi<annotation encoding="application / x-tex">H_i< / annotation>< / semantics>< / com:Math>; in another embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is halogen; in another embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another embodiment, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0062] In one embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form <com:Math><semantics>−(CH2)pY<annotation encoding="application / x-tex">-(CH_2)_pY< / annotation>< / semantics>< / com:Math> -, <com:Math><semantics>−Y(CH2)p<annotation encoding="application / x-tex">-Y(CH_2)_p< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−Y(CH2)pZ<annotation encoding="application / x-tex">-Y(CH_2)_pZ< / annotation>< / semantics>< / com:Math>- group; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form -(CH<com:Sub>2< / com:Sub>)<com:Sub>p< / com:Sub>Y-; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form -Y (CH<com:Sub>2< / com:Sub>)<com:Sub>p< / com:Sub>-; in another embodiment, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> together form -Y (CH<com:Sub>2< / com:Sub>)<com:Sub>p< / com:Sub>Z-.

[0063] In more specific embodiments, p is 1, 2, 3, 4 or 5; in another specific embodiment, p is 1; in another specific embodiment, p is 2; in another specific embodiment, p is 3; in another specific embodiment, p is 4; in another specific embodiment, p is 5.

[0064] In more specific embodiments, Y is selected from O, S, NH or chemical bond; in another specific embodiment, Y is O; in another specific embodiment, Y is S; in another specific embodiment, Y is NH; in another specific embodiment, Y is a chemical bond.

[0065] In more specific embodiments, Z is selected from O, S, NH or chemical bond; in another specific embodiment, Z is O; in another specific embodiment, Z is S; in another specific embodiment, Z is NH; in another specific embodiment, Z is a chemical bond.

[0066] R' C

[0067] In one embodiment, R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another embodiment, R' is H; in another embodiment, <com:Math><semantics>R*<annotation encoding="application / x-tex">R^*< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R*<annotation encoding="application / x-tex">R^*< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, R' is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0068] L

[0069] In one embodiment, L is selected from <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R32)−C(O)−<annotation encoding="application / x-tex">-N(R_3^2)-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−O−C(O)−<annotation encoding="application / x-tex">-O-C(O)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−<annotation encoding="application / x-tex">-S(O)_q-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(R)<annotation encoding="application / x-tex">N(R)< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−S(O)0<annotation encoding="application / x-tex">-S(O)_0< / annotation>< / semantics>< / com:Math>-O-, <com:Math><semantics>−O<annotation encoding="application / x-tex">-O< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−S<annotation encoding="application / x-tex">-S< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−N(R″)<annotation encoding="application / x-tex">-N(R'')< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−C1−4<annotation encoding="application / x-tex">-C_{1-4}< / annotation>< / semantics>< / com:Math> alkylene- or <com:Math><semantics>−C2−4<annotation encoding="application / x-tex">-C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene-; in another embodiment, L is <com:Math><semantics>−C(O)<annotation encoding="application / x-tex">-C(O)< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>N(R)<annotation encoding="application / x-tex">N(R)< / annotation>< / semantics>< / com:Math>-; in another embodiment, L is <com:Math><semantics>−C(O)<annotation encoding="application / x-tex">-C(O)< / annotation>< / semantics>< / com:Math>-O-; in another embodiment, L is <com:Math><semantics>−N(R3)<annotation encoding="application / x-tex">-N(R_3)< / annotation>< / semantics>< / com:Math>-C(O)-; in another embodiment, L is <com:Math><semantics>−O−C(O)<annotation encoding="application / x-tex">-O-C(O)< / annotation>< / semantics>< / com:Math>-; in another embodiment, L is <com:Math><semantics>−S(O)q−N(R)<annotation encoding="application / x-tex">-S(O)_q-N(R)< / annotation>< / semantics>< / com:Math>-; in another embodiment, L is <com:Math><semantics>−S(O)q<annotation encoding="application / x-tex">-S(O)_q< / annotation>< / semantics>< / com:Math>- O-; in another embodiment, L is -O-; in another embodiment, L is -S-; in another embodiment, L is -N(<Formule mathématique disponible dans le document PDF, Math available in the PDF document>$\mathbb{R}^{"}$)-; in another embodiment, L is <com:Math><semantics>−C1−4<annotation encoding="application / x-tex">-C_{1-4}< / annotation>< / semantics>< / com:Math> alkylene-; in another embodiment, L is <com:Math><semantics>−C2−4<annotation encoding="application / x-tex">-C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene-.

[0070] In a more specific embodiment, L is <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−N(R)−<annotation encoding="application / x-tex">-S(O)_q-N(R)-< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−S(O)q−O−<annotation encoding="application / x-tex">-S(O)_q-O-< / annotation>< / semantics>< / com:Math>.

[0071] In a more specific embodiment, L is <com:Math><semantics>−C(O)−N(R)<annotation encoding="application / x-tex">-C(O)-N(R)< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>−C(O)−O<annotation encoding="application / x-tex">-C(O)-O< / annotation>< / semantics>< / com:Math>-.

[0072] In more specific embodiments, R is selected from H, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, R is H; in another specific embodiment, R is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another specific embodiment, R is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> 6 haloalkyl; in another specific embodiment, R is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0073] In more specific embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>° is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; in another specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>' is H; in another specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>' is <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>' is <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_{n-}C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl.

[0074] In more specific embodiments, <com:Math><semantics>ℝn<annotation encoding="application / x-tex">\mathbb{R}^{n}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, R'' is H; in another specific embodiment, R'' is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another specific embodiment, R'' is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl.

[0075] In more specific embodiments, q is 0; in another specific embodiment, q is 1; in another specific embodiment, q is 2.

[0076] <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>

[0077] In one embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_{n-}C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n−NRaRb<annotation encoding="application / x-tex">(CH_2)_{n-}NR_aR_b< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CH2)n−ORa<annotation encoding="application / x-tex">(CH_2)_{n-}OR_a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_{n-}C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n−3−<annotation encoding="application / x-tex">(CH_2)_{n-}3-< / annotation>< / semantics>< / com:Math> to 10- membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−1C1−6<annotation encoding="application / x-tex">(CH_2)_{n-1}C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−1C1−6<annotation encoding="application / x-tex">(CH_2)_{n-1}C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a< / com:Sub>R<com:Sub>b< / com:Sub>; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-OR<com:Sub>a< / com:Sub>; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−3−<annotation encoding="application / x-tex">(CH_2)_n-3-< / annotation>< / semantics>< / com:Math> to 10-membered heterocyclyl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−C6−10<annotation encoding="application / x-tex">(CH_2)_{n-}C_{6-10}< / annotation>< / semantics>< / com:Math> aryl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CH2)n−<annotation encoding="application / x-tex">(CH_2)_{n-}< / annotation>< / semantics>< / com:Math>5- to 10- membered heteroaryl; in another embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form -<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene.

[0078] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−5<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, CA <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CR7R8)n−NR8R8<annotation encoding="application / x-tex">(CR_7R_8)_n-NR_8R_8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CR7R8)n−OR8<annotation encoding="application / x-tex">(CR_7R_8)_n-OR_8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-3- to 10-membered heterocyclyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_{m}-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1.6<annotation encoding="application / x-tex">C_{1.6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>NR8Rb<annotation encoding="application / x-tex">NR_8R_b< / annotation>< / semantics>< / com:Math>; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OR8<annotation encoding="application / x-tex">OR_8< / annotation>< / semantics>< / com:Math>; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_{n}-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n−3<annotation encoding="application / x-tex">(CR_7R_8)_{n-3}< / annotation>< / semantics>< / com:Math> to 10-membered heterocyclyl; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n−3<annotation encoding="application / x-tex">(CR_7R_8)_{n-3}< / annotation>< / semantics>< / com:Math> aryl; in another more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl.

[0079] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_{n}-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_{n}-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CR7R8)n−NR8R8<annotation encoding="application / x-tex">(CR_7R_8)_{n}-NR_8R_8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_{n}-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)n−4<annotation encoding="application / x-tex">(CR_7R_8)_{n}-4< / annotation>< / semantics>< / com:Math>- to 7-membered heterocyclyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form -C<com:Sub>1-6< / com:Sub> alkylene-.

[0080] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n−NR8Rb<annotation encoding="application / x-tex">(CR_7R_8)_n-NR_8R_b< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)n−C6−10<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n−5−<annotation encoding="application / x-tex">(CR_7R_8)_n-5-< / annotation>< / semantics>< / com:Math> to 10- membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene.

[0081] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>NR8R8<annotation encoding="application / x-tex">NR_8R_8< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form a <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene.

[0082] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CR7R8)n−C3−4<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl.

[0083] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-5- to 10- membered heteroaryl.

[0084] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, only containing O as heteroatom.

[0085] In a more specific embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CR7R9)n<annotation encoding="application / x-tex">(CR_7R_9)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, only containing O as heteroatom.

[0086] In another embodiment, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7- membered heterocyclyl group.

[0087] m and n

[8800] In one embodiment, m is 0, 1, 2, 3, 4 or 5; in another embodiment, m is 0; in another embodiment, m is 1; in another embodiment, m is 2; in another embodiment, m is 3; in another embodiment, m is 4; in another embodiment, m is 5.

[0089] In one embodiment, n is 0, 1, 2, 3, 4 or 5; in another embodiment, n is 0; in another embodiment, n is 1; in another embodiment, n is 2; in another embodiment, n is 3; in another embodiment, n is 4; in another embodiment, n is 5.

[0090] <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math>

[0091] In one embodiment, <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is C<com:Sub>1-6< / com:Sub> haloalkyl.

[0092] In one embodiment, <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−δ<annotation encoding="application / x-tex">C_{1-\delta}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is C<com:Sub>1-6< / com:Sub> haloalkyl.

[0093] In one embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is D; in another embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0094] In one embodiment, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is D; in another embodiment, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0095] In one embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is D; in another embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0096] In one embodiment, <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is H; in another embodiment, <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is D; in another embodiment, <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; in another embodiment, <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; in another specific embodiment, <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration.

[0097] In another specific embodiment, <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> on the same carbon atom are combined to form = 0.

[0098] Substituent groups of R<com:Sub>3< / com:Sub>

[0099] In one embodiment, R<com:Sub>3< / com:Sub> is optionally substitued with one, two, three or more substituent groups selected from H, D, halogen, CN, OH, =O, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>3-7< / com:Sub> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, -O-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, -O-4- to 7-membered heterocyclyl, <com:Math><semantics>−O−C6−10<annotation encoding="application / x-tex">-O-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−O−5−<annotation encoding="application / x-tex">-O-5-< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>10−<annotation encoding="application / x-tex">10-< / annotation>< / semantics>< / com:Math>membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, -C(O)-C<com:Sub>6-10< / com:Sub> aryl, -C(O)-5- to 10-membered heteroaryl, -S(O)<com:Sub>q< / com:Sub>-C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−S(O)q−C3−7<annotation encoding="application / x-tex">-S(O)_q-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−S(O)q−4<annotation encoding="application / x-tex">-S(O)_q-4< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−S(O)q−C6−10<annotation encoding="application / x-tex">-S(O)_q-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−S(O)q−5−<annotation encoding="application / x-tex">-S(O)_q-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl.

[0100] In one embodiment, R<com:Sub>3< / com:Sub> is optionally substitued with one, two, three or more substituent groups selected from H, D, halogen, CN, OH, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy or -S(O)<com:Sub>0< / com:Sub>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl.

[0101] In one embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted with a group selected from H, D, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy or <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl.

[0102] In one embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted by one or more substituent groups selected from H, D, halogen, CN, OH, =O, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>3-7< / com:Sub> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>−O−C3−7<annotation encoding="application / x-tex">-O-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−O−4−<annotation encoding="application / x-tex">-O-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−O−C6−10<annotation encoding="application / x-tex">-O-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−O−5−<annotation encoding="application / x-tex">-O-5-< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>10−<annotation encoding="application / x-tex">10-< / annotation>< / semantics>< / com:Math>membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, -C(O)-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, -C(O)-5- to 10-membered heteroaryl.

[0103] In one embodiment, R<com:Sub>3< / com:Sub> is optionally substituted by one or more substituent groups selected from H, C D, halogen, CN, OH, =O, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, C<com:Sub>1-6< / com:Sub> alkoxy, C<com:Sub>3-7< / com:Sub> cycloalkyl, -C(O)-C<com:Sub>1-6< / com:Sub> alkyl, - <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or -O-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl.

[0104] In one embodiment, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted with a group selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0105] Any technical solution in any of the above specific embodiments or any combination thereof can be combined with any technical solution in other specific embodiments or any combination thereof. For example, any technical solution of X or any combination thereof can be combined with any technical solution of <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math>, R', L and R<com:Sub>3< / com:Sub>, etc. or any combination thereof. The present disclosure is intended to include the combination of all these technical solutions, which is not listed one by one due to space limitation.

[0106] In more specific embodiments, the present disclosure relates to a compound of formula (II), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (II) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>R*<annotation encoding="application / x-tex">R^*< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0107] In another more specific embodiment, the present disclosure relates to a compound of formula (II), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> haloalkyl; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^{2}< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n−C1−6<annotation encoding="application / x-tex">(CH_2)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, CA <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0108] In another more specific embodiment, the present disclosure relates to a compound of formula (II), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>ℝ*<annotation encoding="application / x-tex">\mathbb{R}^*< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; alternatively, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0109] In another more specific embodiment, the present disclosure relates to a compound of formula (II), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; wherein m is 0, 1, 2 or 3; n is 0, 1, 2 or 3.

[0110] In another more specific embodiment, the present disclosure relates to a compound of formula (III), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (III) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; CA L is selected from -O-, -S-, -N(R'')-, -C<com:Sub>1-4< / com:Sub> alkylene- or -C<com:Sub>2-4< / com:Sub> alkenylene-; alternatively, L is -O-; wherein R'' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_{n}-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n−4−<annotation encoding="application / x-tex">(CH_2)_{n}-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>(CH2)n−C6−10<annotation encoding="application / x-tex">(CH_2)_{n}-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n−5−<annotation encoding="application / x-tex">(CH_2)_{n}-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; alternatively, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n−4<annotation encoding="application / x-tex">(CH_2)_{n-4}< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>(CH2)n−6−10<annotation encoding="application / x-tex">(CH_2)_{n-6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n−5<annotation encoding="application / x-tex">(CH_2)_{n-5}< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0111] In another more specific embodiment, the present disclosure relates to a compound of formula (III), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is -O-; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_{n-}C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>(CH2)n−4<annotation encoding="application / x-tex">(CH_2)_{n-4}< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0112] In another more specific embodiment, the present disclosure relates to a compound of formula (III), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; alternatively, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is O; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 6- membered heteroaryl containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0113] In another more specific embodiment, the present disclosure relates to a compound of formula (III), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; alternatively, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>𝑪I<annotation encoding="application / x-tex">\mathbf{C}I< / annotation>< / semantics>< / com:Math> H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; L is -O-; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0114] In another more specific embodiment, the present disclosure relates to a compound of formula (IV), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (|V|) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; or, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0115] In another more specific embodiment, the present disclosure relates to a compound of formula (IV), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m−C1−6<annotation encoding="application / x-tex">(CH_2)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n−C3−7<annotation encoding="application / x-tex">(CH_2)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CH2)m<annotation encoding="application / x-tex">(CH_2)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CH2)n<annotation encoding="application / x-tex">(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; or, R<com:Sub>3< / com:Sub>, R<com:Sub>3< / com:Sub>' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

[0116] In another more specific embodiment, the present disclosure relates to a compound of formula (V), CA or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (V) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; L is <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)q−N(R)−<annotation encoding="application / x-tex">-S(O)_q-N(R)-< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−S(O)q−O−<annotation encoding="application / x-tex">-S(O)_q-O-< / annotation>< / semantics>< / com:Math>; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; q is 0, 1 or 2; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkoxy, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a< / com:Sub>R<com:Sub>b< / com:Sub>, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>3-7< / com:Sub> cycloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n−5<annotation encoding="application / x-tex">(CR_7R_8)_{n-5}< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene-; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substitued with a group selected from H, D, halogen, CN, OH, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, 5- to 10-membered heteroaryl, <com:Math><semantics>(CR7R8)n−1<annotation encoding="application / x-tex">(CR_7R_8)_{n-1}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy or <com:Math><semantics>−S(O)q−C1−6<annotation encoding="application / x-tex">-S(O)_q-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substitued with one or more D, up to complete deuteration.

[0117] In another more specific embodiment, the present disclosure relates to a compound of formula (V), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; CA L is <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−O−<annotation encoding="application / x-tex">-C(O)-O-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)0−N(R)−<annotation encoding="application / x-tex">-S(O)_0-N(R)-< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−S(O)0−O−<annotation encoding="application / x-tex">-S(O)_0-O-< / annotation>< / semantics>< / com:Math>; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; q is 0, 1 or 2; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>NR0R0<annotation encoding="application / x-tex">NR_0R_0< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_{n^-}C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)n−C6−10<annotation encoding="application / x-tex">(CR_7R_8)_{n^-}C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n−5<annotation encoding="application / x-tex">(CR_7R_8)_{n^-}5< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form -C<com:Sub>1-6< / com:Sub> alkylene-; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R_b< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted with a group selected from H, D, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy or <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl.

[0118] In another more specific embodiment, the present disclosure relates to a compound of formula (V), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; L is <com:Math><semantics>−C(O)−N(R)<annotation encoding="application / x-tex">-C(O)-N(R)< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>−C(O)−O<annotation encoding="application / x-tex">-C(O)-O< / annotation>< / semantics>< / com:Math>-; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CR7R8)n−NR8R8<annotation encoding="application / x-tex">(CR_7R_8)_n-NR_8R_8< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; or <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is connected to R to form a <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkylene; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>Ra<annotation encoding="application / x-tex">R_a< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; R<com:Sub>7< / com:Sub> and R<com:Sub>8< / com:Sub> are independently selected from H or D; R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> are independently selected from H or D; wherein <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted with a group selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0119] In another more specific embodiment, the present disclosure relates to a compound of formula (V), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>ℝ*<annotation encoding="application / x-tex">\mathbb{R}^*< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; L is <com:Math><semantics>−C(O)−N(R)−<annotation encoding="application / x-tex">-C(O)-N(R)-< / annotation>< / semantics>< / com:Math>; wherein R is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−4<annotation encoding="application / x-tex">C_{3-4}< / annotation>< / semantics>< / com:Math> cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R<com:Sub>7< / com:Sub> and R<com:Sub>8< / com:Sub> are independently selected from H or D; R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> are independently selected from H or D.

[0120] In another more specific embodiment, the present disclosure relates to a compound of formula (VI), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (VI) wherein X is N or <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; alternatively, X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; alternatively, <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>ℝ*<annotation encoding="application / x-tex">\mathbb{R}^*< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m−C1−6<annotation encoding="application / x-tex">(CR_7R_8)_m-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>(CR7R8)n−C3−7<annotation encoding="application / x-tex">(CR_7R_8)_n-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>(CR7R8)m−4<annotation encoding="application / x-tex">(CR_7R_8)_m-4< / annotation>< / semantics>< / com:Math>- to 7- membered heterocyclyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_{n}< / annotation>< / semantics>< / com:Math>-5- to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; or R<com:Sub>7< / com:Sub> and R<com:Sub>8< / com:Sub> on the same carbon atom are combined to form =O; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R₃ is optionally substituted by one or more substituent groups selected from H, D, halogen, CN, OH, =O, NR<com:Sub>c< / com:Sub>R<com:Sub>d< / com:Sub>, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, 4- to 7-membered heterocyclyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, ( 5- to 10-membered heteroaryl, -O-C<com:Sub>3-7< / com:Sub> cycloalkyl, -O-4- to 7-membered heterocyclyl, -O-C<com:Sub>6-10< / com:Sub> aryl, -O-5- to 10-membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7- membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−C(O)−5<annotation encoding="application / x-tex">-C(O)-5< / annotation>< / semantics>< / com:Math>- to 10-membered heteroaryl; wherein <com:Math><semantics>Rc<annotation encoding="application / x-tex">R_c< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; <com:Math><semantics>Rd<annotation encoding="application / x-tex">R_d< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl; wherein the alkyl, haloalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substitued with substituent groups selected from H, D, CN, OH, =O, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> 7 cycloalkyl, 4- to 7-membered heterocyclyl, C<com:Sub>6-10< / com:Sub> aryl, 5- to 10-membered heteroaryl, -O-C<com:Sub>3-7< / com:Sub> cycloalkyl, -O- 4- to 7-membered heterocyclyl, <com:Math><semantics>−O−C6−10<annotation encoding="application / x-tex">-O-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−O−5−<annotation encoding="application / x-tex">-O-5-< / annotation>< / semantics>< / com:Math> to 10-membered heteroaryl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−4−<annotation encoding="application / x-tex">-C(O)-4-< / annotation>< / semantics>< / com:Math> to 7-membered heterocyclyl, <com:Math><semantics>−C(O)−C6−10<annotation encoding="application / x-tex">-C(O)-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>−C(O)−5−<annotation encoding="application / x-tex">-C(O)-5-< / annotation>< / semantics>< / com:Math> to 10- membered heteroaryl, or substitued with one or more D, up to complete deuteration.

[0121] In another more specific embodiment, the present disclosure relates to a compound of formula (VI), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein R<com:Sub>3< / com:Sub> is optionally substituted by one or more substituent groups selected from H, D, halogen, CN, OH, =O, <com:Math><semantics>NRcRd<annotation encoding="application / x-tex">NR_cR_d< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−7<annotation encoding="application / x-tex">C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−C(O)−C1−6<annotation encoding="application / x-tex">-C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>−O−C3−7<annotation encoding="application / x-tex">-O-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>−O−C3−7<annotation encoding="application / x-tex">-O-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl or <com:Math><semantics>−O−C3−7<annotation encoding="application / x-tex">-O-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl o <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl; wherein <com:Math><semantics>Rc<annotation encoding="application / x-tex">R_c< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; <com:Math><semantics>Rd<annotation encoding="application / x-tex">R_d< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>−C(O)−C3−7<annotation encoding="application / x-tex">-C(O)-C_{3-7}< / annotation>< / semantics>< / com:Math> cycloalkyl; wherein the alkyl, haloalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substitued with substituent groups selected from H, D, CN, =O, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy or -C(O)- <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, or substitued with one or more D, up to complete deuteration.

[0122] In another more specific embodiment, the present disclosure relates to a compound of formula (VI), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; <com:Math><semantics>ℝ*<annotation encoding="application / x-tex">\mathbb{R}^*< / annotation>< / semantics>< / com:Math> is selected from H, <com:Math><semantics>ℂ1−5<annotation encoding="application / x-tex">\mathbb{C}_{1-5}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>ℂ1−5<annotation encoding="application / x-tex">\mathbb{C}_{1-5}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>ℂ1−6<annotation encoding="application / x-tex">\mathbb{C}_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R<com:Sub>3< / com:Sub> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> haloalkyl, <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-C<com:Sub>3-7< / com:Sub> cycloalkyl or <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; CA <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is optionally substituted with a group selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy.

[0123] In another more specific embodiment, the present disclosure relates to a compound of formula (VI), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: wherein X is <com:Math><semantics>C(Rx)<annotation encoding="application / x-tex">C(R_x)< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>Rx<annotation encoding="application / x-tex">R_x< / annotation>< / semantics>< / com:Math> is selected from H or halogen; R' is selected from H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>(CR7R8)m<annotation encoding="application / x-tex">(CR_7R_8)_m< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or <com:Math><semantics>(CR7R8)n<annotation encoding="application / x-tex">(CR_7R_8)_n< / annotation>< / semantics>< / com:Math>-4- to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are independently selected from H, D, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics&g...

Claims

1. A compound of formula (X), or a tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof: [Image disponible dans le document PDF, Image available in the PDF document] (X) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R 1 R_1 is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R 2 R_2 is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; or R 1 R_1 and R 2 R_2 together form -(CH 2 ) p Y-, -Y(CH 2 ) p - or -Y(CH 2 ) p Z- group; wherein p is 1, 2, 3, 4 or 5; Y is O, S, NH or chemical bond; Z is O, S, NH or chemical bond; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − O − -C(O)-O- , − N ( R 3 ′ ) − C ( O ) − -N(R_3')-C(O)- , − O − C ( O ) − -O-C(O)- , − S ( O ) q − N ( R ) − -S(O)_q-N(R)- , − S ( O ) q − O − -S(O)_q-O- , − O − -O- , − S − -S- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( R ) − -C(O)-N(R)- , − C ( O ) − N ( -C(O)-N( N ( R ″ ) N(R'') -, - C 1 − 4 C_{1-4} alkylene- or - C 2 − 4 C_{2-4} alkenylene-; wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 ' is H, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; R" is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; q is 0, 1 or 2; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, (CH 2 ) n -NR a R b , (CH 2 ) n -OR a , (CH 2 ) n -C 3-7 cycloalkyl, (CH 2 ) n -3- to 10-membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n -5- to 10-membered heteroaryl; or R 3 R_3 is connected to R to form - C 1 − C_{1-} 6 alkylene-; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R a R_a is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R b R_b is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 5 R_5 and R 6 R_6 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; wherein R 3 is optionally substituted by one or more substituent groups of H, D, halogen, CN, OH, =O, NR c R d , C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, C 1 − 6 C_{1-6} alkoxy, C 3 − 7 C_{3-7} cycloalkyl, 4- to 7-membered heterocyclyl, C 6-10 aryl, 5- to 10-membered heteroaryl, (CH 2 ) m -C 1-6 alkyl, (CH 2 ) m -C 1-6 haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, − O -O - C 3 − 7 C_{3-7} cycloalkyl, − O -O -4- to 7- membered heterocyclyl, -O-C 6-10 aryl, -O-5- to 10-membered heteroaryl, -C(O)-C 1-6 alkyl, - C ( O ) C(O) - C 1 − 6 C_{1-6} haloalkyl, − C ( O ) -C(O) - C 3 − 7 C_{3-7} cycloalkyl, − C ( O ) -C(O) -4- to 7-membered heterocyclyl, − C ( O ) -C(O) - C 6 − 10 C_{6-10} aryl, − C ( O ) -C(O) -5- to 10-membered heteroaryl, − S ( O ) q -S(O)_q - C 1 − 6 C_{1-6} alkyl, − S ( O ) q -S(O)_q - C 1 − 6 C_{1-6} haloalkyl, − S ( O ) q -S(O)_q - C 1 − 6 C_{1-6} 6 _6 alkoxy, − S ( O ) q − C 3 − 7 -S(O)_q-C_{3-7} cycloalkyl, − S ( O ) q − 4 − -S(O)_q-4- to 7-membered heterocyclyl, − S ( O ) q − C 6 − 10 -S(O)_q-C_{6-10} aryl or − - S ( O ) q S(O)_q -5- to 10-membered heteroaryl; wherein R c is H, C 1-6 alkyl, C 1-6 haloalkyl, -C(O)-C 3-7 cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, − C ( O ) − C 6 − 10 -C(O)-C_{6-10} aryl or − C ( O ) − 5 -C(O)-5 - to 10-membered heteroaryl; R d R_d is H, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl, − C ( O ) − 4 − -C(O)-4- to 7-membered heterocyclyl, − C ( O ) − C 6 − 10 -C(O)-C_{6-10} aryl or − C ( O ) − 5 -C(O)-5 - to 10-membered heteroaryl; wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkylene and alkenylene are optionally substituted with substituent groups of H, D, CN, OH, =O, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, C 1 − 6 C_{1-6} alkoxy, C 3 − 7 C_{3-7} cycloalkyl, 4- to 7-membered heterocyclyl, C 6-10 aryl, 5- to 10-membered heteroaryl, -O-C 3-7 cycloalkyl, -O-4- to 7- membered heterocyclyl, -O-C 6-10 aryl, -O-5- to 10-membered heteroaryl, -C(O)-C 1-6 alkyl, - C(O)-C 1-6 haloalkyl, -C(O)-C 3-7 cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, -C(O)-C 6-10 aryl or -C(O)-5- to 10-membered heteroaryl, or substituted with one or more D, up to complete deuteration.

2. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, which is a compound of formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (V) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; [Image disponible dans le document PDF, Image available in the PDF document] wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; q is 0, 1 or 2; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 1 − 6 C_{1-6} alkoxy, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkoxy, (CR 7 R 8 ) n -NR a R b , (CR 7 R 8 ) n -C 3-7 cycloalkyl, (CR 7 R 8 ) n -4- to 7-membered heterocyclyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 6 − 10 C_{6-10} aryl or ( C R 7 R 8 ) n (CR_7R_8)_n -5- to 10-membered heteroaryl; or R 3 R_3 is connected to R to form − C 1 − 6 -C_{1-6} alkylene-; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R a R_a is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R b R_b is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 7 R_7 and R 8 R_8 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 5 R_5 and R 6 R_6 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 is optionally substituted with a group of H, D, halogen, CN, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, 4- to 7-membered heterocyclyl, C 6-10 aryl, 5- to 10-membered heteroaryl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 1 − 6 C_{1-6} alkoxy or − S ( O ) q -S(O)_q - C 1 − 6 C_{1-6} alkyl; wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one or more D, up to complete deuteration.

3. The compound of formula (V), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 2, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

4. The compound of formula (V), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 2, wherein X is C ( R x ) C(R_x) , wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; [Image disponible dans le document PDF, Image available in the PDF document] wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; q is 0, 1 or 2; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 1 − 6 C_{1-6} alkoxy, ( C R 7 R 8 ) n (CR_7R_8)_n - N R a R b NR_aR_b , ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 6 − 10 C_{6-10} aryl or ( C R 7 R 8 ) n (CR_7R_8)_n -5- to 10-membered heteroaryl; or R 3 R_3 is connected to R to form - C 1 − 6 C_{1-6} alkylene-; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R a R_a is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R b R_b is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 7 R_7 and R 8 R_8 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 5 R_5 and R 6 R_6 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 R_3 is optionally substituted with a group of H, D, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, C 1-6 alkoxy or C 3-7 cycloalkyl.

5. The compound of formula (V), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 2, wherein X is C ( R x ) C(R_x) , wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; L is − C ( O ) − N ( R ) -C(O)-N(R) - or − C ( O ) − O -C(O)-O -; wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 1 − 6 C_{1-6} alkoxy, ( C R 7 R 8 ) n (CR_7R_8)_n - N R a R b NR_aR_b or ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 4 C_{3-4} cycloalkyl; or R 3 R_3 is connected to R to form a C 1 − 6 C_{1-6} alkylene; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R a R_a is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R b R_b is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 7 and R 8 are independently H or D; R 5 and R 6 are independently H or D; wherein R 3 is optionally substituted with a group of H, D, C 1-6 alkyl, C 1-6 haloalkyl or C 1-6 alkoxy.

6. The compound of formula (V), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 2, wherein X is C ( R x ) C(R_x) , wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; L is − C ( O ) − N ( R ) − -C(O)-N(R)- ; wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 4 C_{3-4} cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 and R 8 are independently H or D; R 5 and R 6 are independently H or D.

7. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, which is a compound of formula (VI): [Image disponible dans le document PDF, Image available in the PDF document] (VI) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n -4- to 7-membered heterocyclyl, ( C R 7 R 8 ) n (CR_7R_8)_n -C 6-10 aryl or ( C R 7 R 8 ) n (CR_7R_8)_n -5- to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 R_7 and R 8 R_8 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; or R 7 R_7 and R 8 R_8 on the same carbon atom are combined to form =O; R 5 and R 6 are independently H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 is optionally substituted by one or more substituent groups of H, D, halogen, CN, OH, =O, NR c R d , C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, C 1 − 6 C_{1-6} alkoxy, C 3 − 7 C_{3-7} cycloalkyl, 4- to 7-membered heterocyclyl, C 6-10 aryl, 5- to 10-membered heteroaryl, -O-C 3-7 cycloalkyl, -O-4- to 7- membered heterocyclyl, -O-C 6-10 aryl, -O-5- to 10-membered heteroaryl, -C(O)-C 1-6 alkyl, - C(O)-C 1-6 haloalkyl, -C(O)-C 3-7 cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, -C(O)-C 6-10 aryl, or − C ( O ) -C(O) -5- to 10-membered heteroaryl; wherein R c is H, C 1-6 alkyl, C 1-6 haloalkyl, -C(O)-C 3-7 cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, − C ( O ) − C 6 − 10 -C(O)-C_{6-10} aryl or − C ( O ) − 5 -C(O)-5 - to 10-membered heteroaryl; R d R_d is H, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl, − C ( O ) − 4 − -C(O)-4- to 7-membered heterocyclyl, − C ( O ) − C 6 − 10 -C(O)-C_{6-10} aryl or − C ( O ) − 5 -C(O)-5 - to 10-membered heteroaryl; wherein the alkyl, haloalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with substituent groups of H, D, CN, OH, =O, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-7 cycloalkyl, 4- to 7-membered heterocyclyl, C 6-10 aryl, 5- to 10- membered heteroaryl, -O-C 3-7 cycloalkyl, -O-4- to 7-membered heterocyclyl, -O-C 6-10 aryl, - O-5- to 10-membered heteroaryl, − C ( O ) − C 1 − 6 -C(O)-C_{1-6} alkyl, − C ( O ) − C 1 − 6 -C(O)-C_{1-6} haloalkyl, − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl, -C(O)-4- to 7-membered heterocyclyl, -C(O)- C 6 − 10 C_{6-10} aryl, or -C(O)-5- to 10-membered heteroaryl, or substituted with one or more D, up to complete deuteration.

8. The compound of formula (VI), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 7, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

9. The compound of formula (VI), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 7, wherein R 3 is optionally substituted by one or more substituent groups of H, D, halogen, CN, OH, =O, N R c R d NR_cR_d , C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, C 1 − 6 C_{1-6} alkoxy, C 3 − 7 C_{3-7} cycloalkyl, − C ( O ) − C 1 − 6 -C(O)-C_{1-6} alkyl, − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl or − O − C 6 − 10 -O-C_{6-10} aryl; wherein R c R_c is H, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl; R d R_d is H, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or − C ( O ) − C 3 − 7 -C(O)-C_{3-7} cycloalkyl; wherein the alkyl, haloalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with substituent groups of H, D, CN, =O, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkyl, or substituted with one or more D, up to complete deuteration.

10. The compound of formula (VI), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 7, wherein X is C ( R x ) C(R_x) ; wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n -4- to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 and R 8 are independently H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 5 and R 6 are independently H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 is optionally substituted with a group of H, D, C 1-6 alkyl, C 1-6 haloalkyl or C 1-6 alkoxy.

11. The compound of formula (VI), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 7, wherein X is C ( R x ) C(R_x) ; wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n -4- to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 R_7 and R 8 R_8 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 5 R_5 and R 6 R_6 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 is optionally substituted with a group of H, D, C 1-6 alkyl, C 1-6 haloalkyl or C 1-6 alkoxy.

12. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, which is a compound of formula (VII): [Image disponible dans le document PDF, Image available in the PDF document] (VII) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C R 7 R 8 ) n (CR_7R_8)_n -4- to 7-membered heterocyclyl, ( C R 7 R 8 ) n (CR_7R_8)_n -C 6-10 aryl or ( C R 7 R 8 ) n (CR_7R_8)_n -5- to 10-membered heteroaryl; R 3 R_3 ' is H, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 and R 8 are independently H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; or R 7 R_7 and R 8 R_8 on the same carbon atom are combined to form =O; R 5 and R 6 are independently H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the C 1-6 alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 R_3 is optionally substituted with one or more groups of H, D, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy.

13. The compound of formula (VII), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 12, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

14. The compound of formula (VII), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 12, wherein X is C ( R x ) C(R_x) , wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl; R 3 R_3 ' is H, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} alkyl, ( C R 7 R 8 ) m (CR_7R_8)_m - C 1 − 6 C_{1-6} haloalkyl or ( C R 7 R 8 ) n (CR_7R_8)_n - C 3 − 7 C_{3-7} cycloalkyl; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; R 7 R_7 and R 8 R_8 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1-6 haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; R 5 R_5 and R 6 R_6 are independently H, D, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl, wherein the C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 D, up to complete deuteration; wherein R 3 is optionally substituted with one or more groups of H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl or C 1 − 6 C_{1-6} alkoxy.

15. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, which is a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R 1 R_1 is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R 2 R_2 is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; or R 1 R_1 and R 2 R_2 together form -(CH 2 ) p Y-, -Y(CH 2 ) p - or -Y(CH 2 ) p Z- group; wherein p is 1, 2, 3, 4 or 5; Y is O, S, NH or chemical bond; Z is O, S, NH or chemical bond; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is − C ( O ) − N ( R ) − -C(O)-N(R)- , − N ( R 3 ′ ) − C ( O ) − -N(R_3')-C(O)- , − O − -O- , − S − -S- , − N ( R ″ ) − -N(R'')- , − C 1 − 4 -C_{1-4} alkylene- or − C 2 − 4 -C_{2-4} alkenylene-; wherein R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 ' is H, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; R" is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C H 2 ) n (CH_2)_n -3- to 10-membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n - 5- to 10-membered heteroaryl; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

16. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 15, which is a compound of formula (II): [Image disponible dans le document PDF, Image available in the PDF document] (II) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C H 2 ) n (CH_2)_n -4- to 7-membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n -5- to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

17. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 16, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

18. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 16, wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, ( C H 2 ) n (CH_2)_n - C 3 − 4 C_{3-4} cycloalkyl or ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

19. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 18, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

20. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 16, wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 4 C_{3-4} cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

21. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 20, wherein X is C ( R x ) C(R_x) , R x R_x is H or halogen, and R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 4 C_{3-4} cycloalkyl.

22. The compound of formula (II), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 16, wherein X is C ( R x ) C(R_x) ; wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 4 C_{3-4} cycloalkyl; wherein m is 0, 1, 2 or 3; n is 0, 1, 2 or 3.

23. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 15, which is a compound of formula (III): [Image disponible dans le document PDF, Image available in the PDF document] (III) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is -O-, -S-, -N(R'')-, -C 1-4 alkylene- or -C 2-4 alkenylene-; wherein R" is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} alkoxy, ( C H 2 ) n (CH_2)_n - C 1 − 6 C_{1-6} haloalkoxy, ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C H 2 ) n (CH_2)_n -4- to 7-membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n -5- to 10-membered heteroaryl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

24. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 23, wherein X is C ( R x ) C(R_x) , R x R_x is H or halogen, L is -O-, and R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl, ( C H 2 ) n (CH_2)_n -4- to 7-membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n -5- to 10-membered heteroaryl.

25. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 23, wherein X is C ( R x ) C(R_x) ; wherein R x R_x is H or halogen; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is -O-; R 3 R_3 is ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl or ( C H 2 ) n (CH_2)_n -4- to 7-membered heterocyclyl only containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

26. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 23, wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is O; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl, ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl or ( C H 2 ) n (CH_2)_n -5- to 6- membered heteroaryl containing O as heteroatom; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

27. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 26, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

28. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 23, wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; L is -O-; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

29. The compound of formula (III), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 28, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

30. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 15, which is a compound of formula (IV): [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m − C 1 − 6 (CH_2)_m-C_{1-6} alkyl, ( C H 2 ) m − C 1 − 6 (CH_2)_m-C_{1-6} haloalkyl, ( C H 2 ) n − C 3 − 7 (CH_2)_n-C_{3-7} cycloalkyl, ( C H 2 ) n − 4 − (CH_2)_n-4- to 7- membered heterocyclyl, ( C H 2 ) n (CH_2)_n - C 6 − 10 C_{6-10} aryl or ( C H 2 ) n (CH_2)_n -5- to 10-membered heteroaryl; R 3 R_3 ' is H, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5.

31. The compound of formula (IV), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 30, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

32. The compound of formula (IV), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 30, wherein X is N or C ( R x ) C(R_x) ; wherein R x R_x is H, halogen, C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl or C 1 − 6 C_{1-6} alkoxy; R' is H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; R 3 R_3 is ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; R 3 R_3 ' is H, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} alkyl, ( C H 2 ) m (CH_2)_m - C 1 − 6 C_{1-6} haloalkyl or ( C H 2 ) n (CH_2)_n - C 3 − 7 C_{3-7} cycloalkyl; or, R 3 , R 3 ' and the N atom to which they are attached together form a 4- to 7-membered heterocyclyl group; wherein m is 0, 1, 2, 3, 4 or 5;33. The compound of formula (IV), or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 32, wherein X is C ( R x ) C(R_x) , and R x R_x is H or halogen.

34. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1-33, wherein R' is H.

35. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1-3, 7-9, 12-13, 15-17, 23-24, or 30-31, wherein R 3 R_3 is ( C H 2 ) n (CH_2)_n -4- to 7-membered heterocyclyl and n is 0, 1, 2, or 3.

36. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1-14, wherein R 5 and R 6 are H.

37. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, wherein the compound is: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]38. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, wherein the compound is: [Image disponible dans le document PDF, Image available in the PDF document] HJM-016 •39. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, wherein the compound is: [Image disponible dans le document PDF, Image available in the PDF document] •40. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, wherein the compound is: [Image disponible dans le document PDF, Image available in the PDF document] □JIVI-IU∠ ٠41. The compound, or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof according to claim 1, wherein the compound is: [Image disponible dans le document PDF, Image available in the PDF document] HJM-10442. A pharmaceutical composition, containing the compound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1-41, and pharmaceutically acceptable excipient(s).

43. The pharmaceutical composition according to claim 42, which is used in combination with immune checkpoint inhibitors.

44. The pharmaceutical composition according to claim 43, wherein the immune checkpoint inhibitors are PD-1, PD-L1, or CTLA-4 antibodies.

45. Use of the compound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1-41, or the pharmaceutical composition as defined in claim 42, 43 or 44 in the manufacture of a medicament for the treatment and / or prevention of an EED- and / or PRC2-mediated disease.

46. The compound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1-41, or the pharmaceutical composition as defined in claim 42, 43 or 44 for use in the treatment and / or prevention of an EED- and / or PRC2-mediated disease.

47. The use according to claim 45 or the compound or pharmaceutical composition for use according to claim 46, wherein the EED- and / or PRC2-mediated disease is a tumor-related disease, an immunodeficiency disease or an autoimmune disease.

48. The use or the compound or pharmaceutical composition for use according to claim 47, wherein, the tumor-related disease is diffuse large B-cell lymphoma, follicular lymphoma, leukemia, multiple myeloma, mesothelioma, gastric cancer, malignant rhabdomyoma, liver cancer, prostate cancer, breast cancer, bile duct and gallbladder cancer, bladder cancer, brain tumors, cervical cancer, colon cancer, melanoma, endometrial cancer, esophageal cancer, head and neck cancer, lung cancer, nasopharyngeal cancer, ovarian cancer, pancreatic cancer, renal cell cancer, rectal cancer, thyroid cancer, parathyroid tumor, uterine tumor and soft tissue sarcoma; wherein the immunodeficiency disease or autoimmune disease are systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, aplastic anemia due to autoimmunity, or rejection reaction due to organ transplantation.

49. The use or the compound or pharmaceutical composition for use according to claim 48, wherein the brain tumors are neuroblastoma, schwannoma, glioma, glioblastoma or astrocytoma.

50. Use of the comound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1-41, or the pharmaceutical composition as defined in claim 42, 43 or 44 in the manufacture of a medicament for tumor immunization.

51. The compound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1-41, or the pharmaceutical composition as defined in claim 42, 43 or 44 for use in tumor immunization.

52. A drug combination, comprising the compound or the tautomer, stereoisomer, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof as defined in any one of claims 1- 41, or the pharmaceutical composition as defined in claim 42, 43 or 44, and immune checkpoint inhibitor(s).