US 12,258,317 B2
Isoquinolinone compound for inhibiting ssao/vap-1, and use thereof
Zheng Gu, Dongguan (CN); Jianhao Li, Dongguan (CN); Weihua Wang, Dongguan (CN); Haoxiong Qin, Dongguan (CN); and Xinshan Deng, Dongguan (CN)
Assigned to SUNSHINE LAKE PHARMA CO., LTD., Dongguan (CN)
Appl. No. 17/608,842
Filed by SUNSHINE LAKE PHARMA CO., LTD., Guangdong (CN)
PCT Filed May 20, 2020, PCT No. PCT/CN2020/091184
§ 371(c)(1), (2) Date Nov. 4, 2021,
PCT Pub. No. WO2020/233583, PCT Pub. Date Nov. 26, 2020.
Claims priority of application No. 201910418254.8 (CN), filed on May 20, 2019.
Prior Publication US 2022/0315536 A1, Oct. 6, 2022
Int. Cl. C07D 217/24 (2006.01); A61P 1/16 (2006.01); C07D 401/06 (2006.01); C07F 9/38 (2006.01); C07F 9/40 (2006.01)
CPC C07D 217/24 (2013.01) [A61P 1/16 (2018.01); C07D 401/06 (2013.01); C07F 9/3817 (2013.01); C07F 9/4006 (2013.01)] 20 Claims
 
1. A compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,
R1 is F, Cl, Br or I;
R2 is H, deuterium, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-6 membered heteroaryl or

OG Complex Work Unit Chemistry
each of R3a, R3b and R3c is independently H, deuterium, F, Cl, Br, I, CN, NO2, —COOH, OH, NH2, —C(═O)—C1-6 alkyl, —C(═O)—C1-6 alkoxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl, cyano C1-6 alkyl, carboxy C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heterocyclyl, C6-10 aryl or 5-6 membered heteroaryl;
W is -L-R4 or —(CRaRb)t—P(═O)(R5)(R6);
L is —(CRaRb)p—C(═O)—NRc, —(CRaRb)q—S—, —(CRaRb)q—S(═O)—, —(CRaRb)s—S(═O)2—, —(CRaRb)q—S(═O)2—NRc— or —(CRaRb)q—S(═O)—NRc—;
each of q, p, s and t is independently 0, 1, 2, 3, 4 or 5;
each of Ra, Rb and Rc is independently H, deuterium, F, Cl, Br, I, CN, NO2, —COOH, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl, cyano C1-6 alkyl, carboxyl C1-6 alkyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-6 membered heteroaryl;
R4 is H, deuterium, C1-8 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-6 membered heteroaryl, wherein each of the C1-8 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl and 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 Ry;
or Rc and R4 together with the nitrogen atom to which they are attached, form 3-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein each of 3-6 membered heterocyclyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 Ry;
each of R5 and R6 is independently OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, C3-6 cycloalkyloxy, C3-6 cycloalkylamino, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, 3-6 membered heterocyclylamino, C6-10 aryl, C6-10 aryloxy, C6-10 arylamino, 5-6 membered heteroaryl, 5-6 membered heteroaryloxy or 5-6 membered heteroarylamino, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, C3-6 cycloalkyloxy, C3-6 cycloalkylamino, 3-6 membered heterocyclyl, 3-6 membered heterocyclyloxy, 3-6 membered heterocyclylamino, C6-10 aryl, C6-10 aryloxy, C6-10 arylamino, 5-6 membered heteroaryl, 5-6 membered heteroaryloxy and 5-6 membered heteroarylamino is independently unsubstituted or substituted with 1, 2, 3 or 4 Ry;
or R5 and R6 together with the phosphorus atom to which they are attached, form 3-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein each of 3-6 membered heterocyclyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 Ry;
each Ry is independently deuterium, F, Cl, Br, I, CN, NO2, —COOH, OH, NH2, —SH, —C(═O)—C1-6 alkyl, —C(═O)—C1-6 alkoxy, —S(═O)2—C1-6 alkyl, —S(═O)2—C1-6 alkylamino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl, cyano C1-6 alkyl, carboxy C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heterocyclyl, C6-10 aryl or 5-6 membered heteroaryl.