US 12,435,060 B2
Acylamino bridged heterocyclic compound, and composition and application thereof
Qiang Zhang, Beijing (CN); Yansheng Liu, Beijing (CN); Xingfu Li, Beijing (CN); Shaohua Zhang, Beijing (CN); and Chenming Hu, Beijing (CN)
Assigned to BEIJING SCITECH-MQ PHARMACEUTICALS LIMITED, Beijing (CN)
Appl. No. 17/425,496
Filed by BEIJING SCITECH-MQ PHARMACEUTICALS LIMITED, Beijing (CN)
PCT Filed Jan. 17, 2020, PCT No. PCT/CN2020/072738
§ 371(c)(1), (2) Date Jul. 23, 2021,
PCT Pub. No. WO2020/151589, PCT Pub. Date Jul. 30, 2020.
Claims priority of application No. 201910071476.7 (CN), filed on Jan. 25, 2019; and application No. 202010027582.8 (CN), filed on Jan. 10, 2020.
Prior Publication US 2023/0026425 A1, Jan. 26, 2023
Int. Cl. C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/12 (2006.01)
CPC C07D 401/12 (2013.01) [C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/12 (2013.01)] 23 Claims
 
1. A compound of formula (I), or pharmaceutically acceptable salts, diastereomers, enantiomers, solvates or prodrugs thereof,

OG Complex Work Unit Chemistry
wherein, in formula (I),
Q is NH, O or S;
A1, A2, and A3 are each independently selected from N or CR4 and at least one of A1, A2, and A3 is N, R4 is H, F, Cl or methyl;
R1 is C3-C8 cycloalkyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, oxo (═O) and —NRaRb,
or 4- to 8-membered heteroalicyclic group, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, oxo (═O) and —NRaRb,
or aryl or heteroaryl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C10 alkyl, halogen, C3-C8 cycloalkyl, halogenated C1-C10 alkyl, cyano, hydroxyl, C1-C6 alkylthio, —SO2—R5, —SO—R5, —CO—R5, —CONH—R5, —NHCO—R5, —R′—COO—R″, —NRaRb, 4- to 8-membered heteroalicyclic group, C2-C6 alkynyl, C2-C6 alkenyl, C1-C3 alkoxy C1-C6 alkylthio, C1-C10 alkyl substituted with hydroxyl and/or C1-C6 alkoxy, C3-C8 cycloalkyl C1-C6 alkyl, (C3-C8 cycloalkyl)-O—(C1-C6 alkyl), C1-C6 alkyl substituted with 4- to 8-membered heteroalicyclic group, and —O—R6,
the aryl group is a monocyclic or bicyclic group containing 6 to 12 carbon ring atoms and having at least one aromatic ring, the heteroaryl is a monocyclic or bicyclic group having 5 to 10 ring atoms and containing 1 to 3 heteroatoms selected from N, O, or S as ring atoms, the 4- to 8-membered heteroalicyclic group is a 4- to 8-membered heteroalicyclic group containing 1 to 2 atoms selected from N, O, or S as ring atoms,
R5 is hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkyl substituted with hydroxyl, C3-C8 cycloalkyl, or C1-C6 alkyl substituted with 4- to 8-membered heteroalicyclic group,
R6 is C1-C10 alkyl, C3-C8 cycloalkyl, 4- to 8-membered heteroalicyclic group, or C1-C10 alkyl which is substituted with 1 to 3 substituents selected from the group consisting of hydroxyl, C1-C6 alkoxy, cyano, —NRaRb, C3-C8 cycloalkyloxy, —CONH—R5, C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with hydroxyl and/or C1-C4 alkyl, carboxylic, halogen, halogenated C1-C6 alkoxy, —SO2—R5, —SO—R5, —CO—R5, C2-C6 alkynyl, C2-C6 alkenyl, C1-C4 alkoxy C1-C6 alkoxy, 4- to 8-membered heteroalicyclic group, 4- to 8-membered heteroalicyclic group substituted with oxo, 4- to 8-membered heteroalicyclic group substituted with hydroxyl and/or C1-C4 alkyl, and C1-C6 alkylthio,
R′ is C2-C6 alkenylene, or C1-C6 alkylene,
R″ is hydrogen, C1-C6 alkyl, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkyl substituted with hydroxyl, C3-C8 cycloalkyl, or C1-C6 alkyl substituted with 4- to 8-membered heteroalicyclic group,
Ra and Rb are each independently selected from hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkyl substituted with C1-C6 alkoxy, C1-C6 alkyl substituted with hydroxyl, C3-C8 cycloalkyl C1-C6 alkyl, C1-C6 alkyl substituted with 4- to 8-membered heteroalicyclic group, C1-C6 alkyl substituted with C1-C3 alkylthio, or C1-C6 alkyl substituted with substituted amino or unsubstituted amino, wherein the substituted amino is substituted with mono- or di-C1-C3 alkyl;
R2 is C3-C8 cycloalkyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, oxo (═O) and —NRcRd,
or C7-C12 bridged cyclyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, oxo (═O) and —NRcRd,
or C1-C10 alkyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, cyano, —CONH2, C3-C8 cycloalkyl, and —NRcRd,
or —(CH2)n-Re, wherein Re is aryl or heteroaryl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, C3-C6 cycloalkyl, phenyl, naphthyl, C2-C6 alkynyl, C2-C6 alkenyl, and —NRcRd, wherein n is an integer from 0 to 3,
or —(CH2)m-Rf, wherein Rf is 4- to 8-membered heteroalicyclic group, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C3 acyl, hydroxyl, halogen, trifluoromethyl, cyano, —CONH2, oxo (═O) and —NRcRd, m is an integer from 0 to 3,
the 4- to 8-membered heteroalicyclic group is a 4- to 8-membered heteroalicyclic group containing 1 to 2 atoms selected from N, O, or S as ring atoms,
the aryl group is a monocyclic or bicyclic group containing 6 to 12 carbon ring atoms and having at least one aromatic ring, the heteroaryl is a monocyclic or bicyclic group having 5 to 10 ring atoms and containing 1 to 3 heteroatoms selected from N, O, or S as ring atoms,
Rc and Rd are each independently selected from hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkyl substituted with C1-C6 alkoxy, C1-C6 alkyl substituted with hydroxyl, C3-C8 cycloalkyl C1-C6 alkyl, C1-C6 alkyl substituted with 4- to 8-membered heteroalicyclic group, C1-C6 alkyl substituted with C1-C3 alkylthio, or C1-C6 alkyl substituted with substituted amino or unsubstituted amino, wherein the substituted amino is substituted with mono- or di-C1-C3 alkyl;
R3 is hydrogen, C1-C3 alkyl, hydroxyl, halogen, trifluoromethyl, or cyano.