US 12,234,211 B2
Cycloolefin substituted heteroaromatic compounds and their use
Wei-Guo Su, Shanghai (CN); Guangxiu Dai, Shanghai (CN); and Kun Xiao, Shanghai (CN)
Assigned to HUTCHISON MEDIPHARMA LIMITED, Shanghai (CN)
Filed by HUTCHISON MEDIPHARMA LIMITED, Shanghai (CN)
Filed on May 18, 2022, as Appl. No. 17/747,925.
Application 17/747,925 is a continuation of application No. 16/645,329, granted, now 11,414,390, previously published as PCT/CN2018/104531, filed on Sep. 7, 2018.
Claims priority of application No. 201710801364.3 (CN), filed on Sep. 7, 2017.
Prior Publication US 2022/0372005 A1, Nov. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 251/48 (2006.01); C07D 401/12 (2006.01); C07D 403/04 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 417/12 (2006.01); C07D 471/04 (2006.01); C07F 5/02 (2006.01)
CPC C07D 251/48 (2013.01) [C07D 401/12 (2013.01); C07D 403/04 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 417/12 (2013.01); C07D 471/04 (2013.01); C07F 5/025 (2013.01)] 15 Claims
 
1. A compound of formula (I-1):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, solvate, racemic mixture, enantiomer, diastereomer, or tautomer thereof, wherein
R1 is chosen from H, —OH, halo, C1-6 alkyl, C1-6 alkoxyl, —NH2, —NH (C1-4 alkyl), —N(C1-4 alkyl)2, oxo, or C3-8 cycloalkyl;
each of R2 is independently chosen from H, deuterium, halo, —OH, —NH2, —CN, —SH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, oxo, —OR5, —OCOR5, —NHR5, —N(R5) (C1-4 alkyl), —COR5, —NHCOR5, or 3-8 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S; in which each of said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl or 3-8 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S is optionally substituted with one or more groups chosen from deuterium, halo, —CN, —OH, —SH, —NH2, —NH (C1-4 alkyl), —N(C1-4 alkyl)2, or C1-6 alkoxyl; or two R2, which attach to the same carbon atom, together with the carbon atom they are attached to form a 3-5 membered cycloalkyl which is optionally substituted with one or more halo or deuterium;
R3′ and R4′ are both H;
R3 and R4 are independently chosen from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, 5-12 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S, —C(O)R5, —OR5, or —NHR5, in which each of said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, or 5-12 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S is optionally substituted with one or more R66; provided that R3 and R4 are not H simultaneously; provided that when one of R3 and R4 is optionally substituted phenyl or optionally substituted 5-6 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S, the other one is —OR5 or —NHR5;
or R3 and R3′ are independently chosen from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, 5-12 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S, —C(O)R5, —OR5, or —NHR5, in which each of said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, or 5-12 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S is optionally substituted with one or more R6; R4 and R4′ together with the N atom they are attached to form a 3-8 membered heterocyclic ring containing one or more heteroatoms independently chosen from N, O, and S which is optionally substituted by one or more R6;
R5 is chosen from C1-6 alkyl or C3-8 cycloalkyl, each of which is optionally substituted with one or more groups independently chosen from halo, —CN, —OH, —SH, —NH2, or C1-6 alkoxyl;
each of R6 is independently chosen from deuterium, halo, —CN, —OH, —SH, —NH2, C1-6 alkoxyl, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, or 5-6 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S, in which each of said C1-6 alkoxyl, C1-6 alkyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl containing one or more heteroatoms independently chosen from N, O, and S, phenyl, or 5-6 membered heteroaryl containing one or more heteroatoms independently chosen from N, O, and S is optionally substituted with one or more groups independently chosen from halo, —CN, —OH, —SH, —NH2, C1-6 alkoxyl, C2-6 alkynyl, or C1-6 alkyl;
m is 0, 1, 2, 3, 4, 5, or 6;
n is 0, 1, or 2.