US 12,263,171 B2
7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
Yonglian Zhang, East Brunswick, NJ (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); Elisabeth Hennessy, Cambridge, MA (US); Matthew A. Larsen, Dedham, MA (US); Kun Liu, Needham, MA (US); Ping Liu, Westfield, NJ (US); Umar Faruk Mansoor, Hopkinton, MA (US); Jianping Pan, Monmouth Junction, NJ (US); Christopher W. Plummer, Westfield, NJ (US); Aaron Sather, Melrose, MA (US); Uma Swaminathan, Auburndale, MA (US); and Huijun Wang, Westfield, NJ (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/294,836
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
PCT Filed Nov. 26, 2019, PCT No. PCT/US2019/063146
§ 371(c)(1), (2) Date May 18, 2021,
PCT Pub. No. WO2020/112706, PCT Pub. Date Jun. 4, 2020.
Claims priority of provisional application 62/774,069, filed on Nov. 30, 2018.
Prior Publication US 2023/0054411 A1, Feb. 23, 2023
Int. Cl. A61K 31/519 (2006.01); A61K 31/55 (2006.01); A61K 39/395 (2006.01); C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/55 (2013.01); A61K 39/3955 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01)] 20 Claims
 
1. A compound having a structural Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from H, F, Cl, Br, CN, OH, (C1-C6)alkyl, O(C1-C6)alkyl, and O(C1-C6)haloalkyl;
R2 is selected from H, F, Cl, Br, CN, OH, (C1-C6)alkyl, (C1-C6)haloalkyl, O(C1-C6)alkyl, O(C1-C6)haloalkyl, (C3-C4)cycloalkyl, S(O)2(C1-C6)alkyl, S(O)2(C1-C6)haloalkyl, and 4-5 membered monocyclic heterocycloalkyl comprising 1 or 2 ring nitrogen atoms;
R4 is selected form H, F, Cl, Br, (C1-C6)alkyl, and (C1-C6)haloalkyl,
with the proviso that at least one of R1, R2, or R4 is not H; and
ring A is a moiety selected from:

OG Complex Work Unit Chemistry
wherein:
R3 is selected from:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
each R3A is independently selected from H, F, Cl, (C1-C6)alkyl, (C1-C6)alkyl-OH, (C1-C6)haloalkyl, (C1-C6)alkylNH2, O(C1-C6)alkyl, O(C1-C6)haloalkyl, C(O)(C1-C3)alkyl, (C1-C4)alkylC(O)(C1-C3)alkyl, (C1-C4)alkylO(C1-C3)alkyl, (C1-C4)alkylCH(OH)(C1-C3)alkyl, (C1-C4)alkylS(O)2(C1-C3)alkyl, (C1-C6)alkylC(O)NH(C1-C6)alkyl, (C1-C6)alkylC(O)OH, (C1-C6)alkylC(O)NH(C3-C6)cycloalkyl,

OG Complex Work Unit Chemistry
—(CH2)n(C3-C7)cycloalkyl, and —(CH2)n4-7 membered monocyclic heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from O, N, S, and S(O)2,
wherein said (C3-C7)cycloalkyl, and said 4-7 membered monocyclic heterocycloalkyl are each unsubstituted or substituted with 1, 2, or 3 groups independently selected from F, Cl, OH, oxo, (C1-C6)alkyl, O(C1-C6)alkyl, (C1-C6)haloalkyl, and O(C1-C6)haloalkyl;
n is 0, 1, or 2;
each R3Aa is independently selected from H, (C1-C4)alkyl, O(C1-C4)alkyl, (C1-C4)haloalkyl, O(C1-C4)haloalkyl, and (C3-C4)cycloalkyl;
RA1 is selected from H, and (C1-C4)alkyl;
each RA2 is independently selected from H, F, and (C1-C4)alkyl;
RA3 is selected from H, F, and (C1-C4)alkyl;
RA4 is selected from H and OH; and
RA5 is selected from H, F, and (C1-C4)alkyl.