US 12,466,831 B2
Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use
Zachary G. Brill, Boston, MA (US); Amjad Ali, Freehold, NJ (US); Jared Cumming, Winchester, MA (US); Duane DeMong, Hanover, MA (US); Qiaolin Deng, Edison, NJ (US); Thomas H. Graham, Somerville, MA (US); Rongze Kuang, Green Brook, NJ (US); Yeon-Hee Lim, South San Francisco, CA (US); Christopher W. Plummer, Cranford, NJ (US); Jenny Lorena Rico Duque, Boston, MA (US); Huijun Wang, Westfield, NJ (US); Yonglian Zhang, East Brunswick, NJ (US); and Kake Zhao, Westfield, NJ (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/292,511
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
PCT Filed Nov. 15, 2019, PCT No. PCT/US2019/061622
§ 371(c)(1), (2) Date May 10, 2021,
PCT Pub. No. WO2020/106558, PCT Pub. Date May 28, 2020.
Claims priority of provisional application 62/769,843, filed on Nov. 20, 2018.
Prior Publication US 2021/0395255 A1, Dec. 23, 2021
Int. Cl. C07D 487/04 (2006.01); C07K 16/28 (2006.01)
CPC C07D 487/04 (2013.01) [C07K 16/2818 (2013.01)] 14 Claims
 
1. A compound having a structural Formula (IA) or Formula (IB):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is a moiety selected from (C3-C7)cycloalkyl and C-linked 4-7 membered monocyclic heterocycloalkyl comprising 1 or 2 ring nitrogen atoms,
wherein said (C3-C7)cycloalkyl, said C-linked 4-7 membered monocyclic heterocycloalkyl comprising 1 or 2 ring nitrogen atoms,
wherein each R1A group is independently selected from:
F, Cl, OH, oxo, (C1-C6)alkyl, O(C1-C6)alkyl, (C1-C6)alkyl-OH, (C1-C6)haloalkyl, —O(C1-C6)haloalkyl, (C3-C6)cycloalkyl, C(O)(C3-C6)cycloalkyl, phenyl, and heteroaryl,
wherein said heteroaryl of R1A is unsubstituted or substituted with 1, 2, or 3 R1A1 groups,
wherein each R1A1 group is independently selected from:
F, Cl, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkyl-OH, O(C1-C6)alkyl, O(C1-C6)haloalkyl, (C1-C6)alkyl-CH((C3-C6)cycloalkyl)OH, (C1-C6)alkyl-C(O)N(R1N)2, and (C4-C6)heterocycloalkyl,
wherein said (C1-C6)alkyl and the (C1-C6)alkyl portions of each of said O—(C1-C6)alkyl and said (C1-C6)alkyl-C(O)N(R1N)2 are optionally further substituted with from 1 to 3 R1A2 groups,
wherein each R1A2 group is independently selected from OH, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-OH, heterocycloalkyl, heteroaryl, N(R1N)2; and
each R1N is independently selected from H and (C1-C6)alkyl;
R2 is selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, and (C3-C4)cycloalkyl,
wherein each said (C1-C6)alkyl and (C3-C4)cycloalkyl of R2 is unsubstituted or substituted with 1, 2, or 3 R2A groups,
wherein each R2A group is independently selected from F, Cl, OH, oxo, (C1-C6)alkyl, O(C1-C6)alkyl, (C1-C6)alkyl-OH, and (C1-C6)haloalkyl, and
R3 is selected from phenyl and heteroaryl, wherein said phenyl and said heteroaryl are unsubstituted or substituted with 1, 2, or 3 R3A groups,
wherein each R3A group is independently selected from the group consisting of F, Cl, OH, CN, (C1-C6)alkyl,(C1-C6)haloalkyl, O—(C1-C6)alkyl, and O—(C1-C6)haloalkyl;
provided that, in Formula (IA), when R1 is cyclopropyl which is substituted with phenyl, then each R3A group is independently selected from the group consisting of F, Cl, OH, (C1-C6)alkyl, (C1-C6)haloalkyl, O(C1-C6)alkyl, and O(C1-C6)haloalkyl, and
further provided that, in Formula (IA), R2 is selected from H, (C1-C6)alkyl, and (C2-C6)alkenyl,
wherein each said (C1-C6)alkyl and cyclobutyl of R2 is unsubstituted or substituted with 1, 2, or 3 R2A groups.