US 12,391,692 B2
Spiro ring-containing quinazoline compound
Yuli Xie, Shanghai (CN); Houxing Fan, Shanghai (CN); Gang Cao, Shanghai (CN); and Lihui Qian, Shanghai (CN)
Assigned to WIGEN BOIMEDICINE TECHNOLOGY (SHANGHAI) CO., LTD., Shanghai (CN)
Appl. No. 17/799,060
Filed by WIGEN BIOMEDICINE TECHNOLOGY (SHANGHAI) CO., LTD., Shanghai (CN)
PCT Filed Mar. 23, 2021, PCT No. PCT/CN2021/082251
§ 371(c)(1), (2) Date Aug. 11, 2022,
PCT Pub. No. WO2021/190467, PCT Pub. Date Sep. 30, 2021.
Claims priority of application No. 202010222766.X (CN), filed on Mar. 25, 2020.
Prior Publication US 2023/0128824 A1, Apr. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 239/72 (2006.01); A61K 31/517 (2006.01); A61P 35/00 (2006.01); C07D 471/10 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/10 (2013.01) [A61P 35/00 (2018.01); C07D 519/00 (2013.01); C07B 2200/07 (2013.01); C07B 2200/13 (2013.01)] 7 Claims
 
1. A compound of general formula (1) or pharmaceutically acceptable salts thereof:

OG Complex Work Unit Chemistry
wherein in the general formula (1):
m is an integer of 1 or 2;
n is an integer of 1 or 2;
R1 is H, halogen, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl or C3-C6 cycloalkyl;
R2 is C1-C3 alkyl or halogenated C1-C3 alkyl;
R3 is

OG Complex Work Unit Chemistry
wherein Ra is H or F, Rb is H, F, Cl or Me, Rc is H, F, Cl or Me, Rd is H, F, Cl, NH2, Me or cyclopropyl, and Re, Rf, Rg, Rh, Ri, Rj and Rk are independently H, F, Cl, OH, OMe, NH2, CF3, C1-C3 alkyl or C3-C6 cycloalkyl;
R4 is

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
wherein n1 and n2 are independently integers of 1 or 2, m1, m2, m3 and m4 are independently integers of 0, 1, 2, 3 or 4, and m5 is an integer of 1, 2 or 3; A is —CH2—, —O—, —S—, —SO—, —SO2— or —N(C1-C3 alkyl)-, V is —CH2—, —SO2— or —CO—, and L is —O—, —S—, —SO2—, —SO— or —CO—; X is a 5- to 7-membered heteroaryl or a partially saturated 5- to 7-membered heterocycloalkyl; Y is C3-C6 cycloalkyl, heterocycloalkyl, (C3-C6) cycloalkyl-(C1-C3) alkyl- or heterocycloalkyl-(C1-C3) alkyl-; Rl and Rm are independently C1-C3 alkyl, halogenated C1-C3 alkyl, hydroxyl-substituted C1-C3 alkyl, cyano-substituted C1-C3 alkyl, C3-C6 cycloalkyl, (C1-C3) alkoxy-(C2-C3) alkyl-, (halogenated C1-C3) alkoxy-(C2-C3) alkyl-, (C3-C6) cycloalkyl-(C1-C3) alkyl-; or Rl and Rm, together with a N atom, form 3- to 8-membered heterocycloalkyl, wherein the 3- to 8-membered heterocycloalkyl can be substituted with 1-3 substituents selected from OH, halogen, cyano, C1-C3 alkyl, C3-C6 cycloalkyl, heterocycloalkyl, (C1-C3) alkoxy and (halogenated C1-C3) alkoxy; Rn is C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, heterocycloalkyl, halogenated C1-C3 alkyl, hydroxyl-substituted C1-C3 alkyl, cyano-substituted C1-C3 alkyl, (C1-C3) alkoxy-(C2-C3) alkyl-, (halogenated C1-C3) alkoxy-(C2-C3) alkyl-, (C3-C6) cycloalkyl-(C1-C3) alkyl- or heterocycloalkyl-(C1-C3) alkyl-; and Ro is OH, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy or C3-C6 cycloalkyl.