US 12,466,823 B2
Inhibitor containing bicyclic derivative, preparation method therefor and use thereof
Yidong Su, Shanghai (CN); Jun Wang, Shanghai (CN); and Rudi Bao, Shanghai (CN)
Assigned to SHANGHAI HANSOH BIOMEDICAL CO., LTD., Shanghai (CN); and JIANGSU HANSOH PHARMACEUTICAL GROUP CO., LTD., Shanghai (CN)
Appl. No. 17/610,939
Filed by SHANGHAI HANSOH BIOMEDICAL CO., LTD., Shanghai (CN); and JIANGSU HANSOH PHARMACEUTICAL GROUP CO., LTD., Lianyungang (CN)
PCT Filed May 14, 2020, PCT No. PCT/CN2020/090142
§ 371(c)(1), (2) Date Nov. 12, 2021,
PCT Pub. No. WO2020/228756, PCT Pub. Date Nov. 19, 2020.
Claims priority of application No. 201910400013.0 (CN), filed on May 14, 2019; application No. 201910615987.0 (CN), filed on Jul. 9, 2019; application No. 201910816375.8 (CN), filed on Aug. 30, 2019; application No. 201910895078.7 (CN), filed on Sep. 20, 2019; and application No. 202010177893.2 (CN), filed on Mar. 13, 2020.
Prior Publication US 2022/0259201 A1, Aug. 18, 2022
Int. Cl. C07D 471/04 (2006.01); A61P 35/00 (2006.01); C07D 471/08 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/00 (2018.01); C07D 471/08 (2013.01); C07D 519/00 (2013.01)] 18 Claims
 
1. A compound represented by general formula (IX-B), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
M3 is selected from bond, —O—, —S—, —NH— or —NCH3—;
R18 and R19 are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy, halogen, amino, nitro, hydroxyl, cyano, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl or 5-12 membered heteroaryl;
or, R18 and R19 together with the carbon atoms they are attached to form a C3-8 cycloalkyl or a 3-12 membered heterocyclyl;
R20 is selected from cyano, or C2-6 alkynyl;
or,

OG Complex Work Unit Chemistry
is selected from

OG Complex Work Unit Chemistry
R24 and R25 are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy, halogen, amino, nitro, hydroxyl, cyano, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl, 5-12 membered heteroaryl or —(CH2)n1ORaa;
or, R24 and R25 together with the carbon atoms they are attached to and G2 form a C3-8 cycloalkyl or 3-12 membered heterocyclyl;
r is 0, 1 or 2;
L is selected from bond, —(CH2)n1CRaaRbb—, —(CH2)n1NRaaC(O)(CH2)n2—, —(CH2)n1C(O)(CH2)n2(CRaaRbb)m—, —(CH2)n1C(O)(CRaaRbb)m(CH2)n2—, —(CH2)n1C(O)NRcc(CRaaRbb)n2—, —(CH2)n1(O)(CH2)n2— or —(CH2)n1NRaa(CH2)n2—;
G2 is selected from N or CRaa;
M1 is selected from N or CRaa;
M2 is selected from N or CRaa;
R9 is selected from hydrogen, deuterium, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy, halogen, amino, nitro, hydroxyl, cyano, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl, 5-12 membered heteroaryl or —(CH2)n1ORaa;
Raa, Rbb and Rcc are each independently selected from hydrogen, deuterium, cyano, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, hydroxyl, C3-8 cycloalkyl, 3-12 membered heterocyclyl or C6-14 aryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, hydroxyl, C3-8 cycloalkyl, 3-12 membered heterocylcyl and C6-14 aryl are optionally further substituted by one or more substituents selected from hydrogen, halogen, cyano, hydroxyl, oxo, imino, C1-6 alkyl or C1-6 hydroxyalkyl;
or, any two of Raa, Rbb and Rcc are optionally connected to form a C3-8 cycloalkyl or a 3-12 membered heterocyclyl, wherein the C3-8 cycloalkyl and 3-12 membered heterocyclyl are optionally further substituted by one or more substituents selected from hydrogen, amino, halogen, cyano, hydroxyl, oxo, imino, C1-6 alkyl or C1-6 hydroxyalkyl;
n1 is 0, 1 or 2;
n2 is 0, 1 or 2;
m is 0, 1 or 2; and
s is 0, 1, 2 or 3.
 
11. A pharmaceutical composition comprising a therapeutically effective amount of the compound as defined in claim 1, or the pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.