US 12,325,696 B2
Indazole derivative, preparation method therefor, and pharmaceutical application thereof
Xing Fan, Shanghai (CN); Fanglong Yang, Shanghai (CN); Jingjing Yan, Shanghai (CN); Xiao Wu, Shanghai (CN); Feng He, Shanghai (CN); and Weikang Tao, Shanghai (CN)
Assigned to JIANGSU HENGRUI MEDICINE CO., LTD., Lianyungang (CN); and SHANGHAI HENGRUI PHARMACEUTICAL CO., LTD., Shanghai (CN)
Appl. No. 17/618,767
Filed by JIANGSU HENGRUI MEDICINE CO., LTD., Lianyungang (CN); and SHANGHAI HENGRUI PHARMACEUTICAL CO., LTD., Shanghai (CN)
PCT Filed Jun. 18, 2020, PCT No. PCT/CN2020/096744
§ 371(c)(1), (2) Date Dec. 13, 2021,
PCT Pub. No. WO2020/253762, PCT Pub. Date Dec. 24, 2020.
Claims priority of application No. 201910530981.3 (CN), filed on Jun. 19, 2019.
Prior Publication US 2022/0267304 A1, Aug. 25, 2022
Int. Cl. C07D 401/14 (2006.01); C07D 401/06 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/06 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01)] 20 Claims
 
1. A compound of formula (I) or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
G is CH or N;
Z is selected from the group consisting of a bond, CR5R6, —O—(CH2)t— and —NR7—(CH2)t—;
ring A is selected from the group consisting of cycloalkyl and heterocyclyl;
Ra is selected from the group consisting of —CH2CH═CHC(O)NR8R9, —C(O)CH═CR10R11 and —C(O)C≡CR12;
Rb is selected from the group consisting of hydrogen atom and alkyl;
each R1 is identical or different and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R2 is selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, amino, cyano, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, cycloalkyl, aryl and heteroaryl;
each R3 is identical or different and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, cyano, amino, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, NR13C(O)R14, C(O)NR13R14, SO2R15, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R4 is identical or different and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, cyano, amino, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R5 and R6 are identical or different and are each independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, cyano, amino, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R7 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R8 and R9 are identical or different and are each independently selected from the group consisting of hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
or, R8 and R9 together with the nitrogen atom to which they are attached form a heterocyclyl, wherein the heterocyclyl optionally contains in addition to one nitrogen atom, one to two identical or different heteroatoms selected from the group consisting of N, O and S, and the heterocyclyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, cyano, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R10 and R11 are identical or different and are each independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, cyano, amino, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R12 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R13 and R14 are identical or different and are each independently selected from the group consisting of hydrogen atom, halogen, alkyl, haloalkyl, alkoxy, cyano, amino, nitro, carboxy, formyl, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R15 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
m is 0 or 1;
n is 0, 1, 2 or 3;
q is 0, 1, 2, 3, 4 or 5;
s is 0, 1, 2 or 3; and
t is 0, 1, 2, 3, 4, 5 or 6.