US 12,128,044 B2
Fused tricyclic compounds and uses thereof in medicine
Jianzhou Huang, Dongguan (CN); Qingyun Ren, Dongguan (CN); Jinfeng Xiong, Dongguan (CN); Yang Liu, Dongguan (CN); Xinchang Liu, Dongguan (CN); Siegfried Goldmann, Wuppertal (DE); Yingjun Zhang, Dongguan (CN); Yifeng Wang, Dongguan (CN); Weishun Liu, Dongguan (CN); and Fangcai Yu, Dongguan (CN)
Assigned to SUNSHINE LAKE PHARMA CO., LTD., Guangdong (CN)
Appl. No. 17/266,961
Filed by SUNSHINE LAKE PHARMA CO., LTD., Guangdong (CN)
PCT Filed Aug. 27, 2019, PCT No. PCT/CN2019/102754
§ 371(c)(1), (2) Date Feb. 8, 2021,
PCT Pub. No. WO2020/043080, PCT Pub. Date Mar. 5, 2020.
Claims priority of application No. 201810985779.5 (CN), filed on Aug. 28, 2018; and application No. 201910201731.5 (CN), filed on Mar. 18, 2019.
Prior Publication US 2021/0236493 A1, Aug. 5, 2021
Int. Cl. C07D 471/04 (2006.01); A61K 31/427 (2006.01); A61K 31/429 (2006.01); A61K 31/5025 (2006.01); A61K 31/52 (2006.01); A61K 31/675 (2006.01); A61K 31/7056 (2006.01); A61K 31/7068 (2006.01); A61K 31/7072 (2006.01); A61K 38/20 (2006.01); A61K 38/21 (2006.01); A61P 31/20 (2006.01)
CPC A61K 31/5025 (2013.01) [A61K 31/427 (2013.01); A61K 31/429 (2013.01); A61K 31/52 (2013.01); A61K 31/675 (2013.01); A61K 31/7056 (2013.01); A61K 31/7068 (2013.01); A61K 31/7072 (2013.01); A61K 38/2013 (2013.01); A61K 38/212 (2013.01); A61K 38/215 (2013.01); A61P 31/20 (2018.01); C07D 471/04 (2013.01)] 21 Claims
 
1. A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof, wherein:

OG Complex Work Unit Chemistry
Y is a single bond, —CH2— or —C(═O)—;
Q is a single bond, —O— or —N(R10)—;
R1 is hydrogen, deuterium, fluorine, chlorine, bromine, iodine, OH, —COOH, heterocyclyl consisting of 5-6 ring atoms, heteroaryl consisting of 5-6 ring atoms, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl or RaRbN—, wherein each of the heterocyclyl consisting of 5-6 ring atoms, heteroaryl consisting of 5-6 ring atoms, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-7 cycloalkyl is independently unsubstituted or substituted by 1, 2, 3 or 4 Rv;
R10 is hydrogen, deuterium, C1-6 alkyl or C1-6 haloalkyl, or R10, R1 together with the nitrogen atom to which they are attached form a heterocyclyl consisting of 3 to 6 ring atoms, wherein each of the C1-6 alkyl, C1-6 haloalkyl and heterocyclyl consisting of 3-6 ring atoms is independently unsubstituted or substituted by 1, 2, 3 or 4 substituents selected from —COOH, ═O, tetrazolyl or C1-6 alkyl-OC(═O)—;
R2 is hydrogen, deuterium, halogen, cyano, C1-6 alkyl or C1-6 alkoxy, wherein each of the C1-6 alkyl and C1-6 alkoxy is independently unsubstitued or substituted by 1, 2, 3, or 4 Rw;
R3 is halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 atoms; wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Rx;
each of R4 and R5 is hydrogen, deuterium, C1-6 alkyl, C1-6 alkylamino, C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, C3-7 cycloalkyl and heterocyclyl consisting of 3-12 ring atoms; wherein each of the C1-6 alkyl, C1-6 alkylamino, C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, C3-7 cycloalkyl and heterocyclyl consisting of 3-12 ring atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Ry;
or R4, R5 together with the carbon atom to which they are attached form C3-7 cycloalkyl or heterocyclyl consisting of 3 to 10 ring atoms;
R6 is hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms; wherein each of the C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Rz;
each R7, R8, R9 is independently hydrogen, deuterium, F, Cl, Br, OH, cyano, C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl, heterocyclyl consisting of 3-6 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms; wherein each of the C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl, heterocyclyl consisting of 3-6 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Rj;
each Ra and Rb is independently hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, C3-6 cycloalkyl, C6-10 aryl, heterocyclyl consisting of 3-6 ring atoms, or heteroaryl consisting of 5-10 atoms; wherein each of the C1-6 alkyl, C1-6 alkoxy, C2-6 alkynyl, C2-6 alkenyl, C3-6 cycloalkyl, C6-10 aryl, heterocyclyl consisting of 3-6 ring atoms and heteroaryl consisting of 5-10 atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 substituents selected from F, Cl, Br, CN, OH, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 alkylamino;
each Rv, Rw, Ry, Rz and Rj is independently deuterium, F, Cl, Br, CN, ═O, OH, —COOH, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-6 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 atoms; wherein each of the amino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-6 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Re;
each Rx is independently deuterium, F, Cl, Br, CN, ═O, OH, —COOH, amino, C1-12 alkyl, C1-12 alkoxy, C1-12 alkylthio, C1-12 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 atoms or -L-R11; wherein each of the amino, C1-12 alkyl, C1-12 alkoxy, C1-12 alkylthio, C1-12 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 ring atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Rf;
L is C1-4 alkylene, C1-3 heteroalkylene, —O—, —(C═O)—, —S(═O)q— or —N(R12)—; wherein each of the C1-4 alkylene and C1-3 heteroalkylene is independently unsubstituted or substituted by 1, 2, 3 or 4 Rg;
R11 is C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl or heteroaryl consisting of 5-10 atoms; wherein each of the C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl, heterocyclyl consisting of 3-12 ring atoms, C6-10 aryl and heteroaryl consisting of 5-10 atoms is independently unsubstituted or substituted by 1, 2, 3, or 4 Rh;
each Re, Rf, Rg and Rh is independently F, Cl, Br, CN, OH, ═O, —COOH, —C(═O)O C1-6 alkyl, —S(═O)2—C1-6 alkyl, —S(═O)2—C3-7 cycloalkyl, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C1-12 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, heteroaryl consisting of 5-6 ring atoms, heterocyclyl consisting of 3-6 ring atoms, C1-6 alkoxy C1-4 alkylene or C1-4 alkylamino C1-4 alkylene;
R12 is hydrogen, deuterium, C1-6 alkyl or C1-6 haloalkyl;
q is 0, 1, or 2;
wherein each heterocyclyl is a saturated or partially saturated non-aromatic monocyclic, bicyclic or tricyclic ring system containing from 3 to 12 ring atoms, wherein at least one ring member is selected from nitrogen, sulfur and oxygen; and
wherein each heteroaryl is a monocyclic or bicyclic ring, and independently comprises 1 to 4 heteroatoms independently selected from nitrogen, sulfur and oxygen.