US 11,970,479 B2
3-(1H-pyrazol-4-yl)pyridine allosteric modulators of the M4 muscarinic acetylcholine receptor
John J. Acton, III, Cranford, NJ (US); Melissa Egbertson, Ambler, PA (US); Xiaolei Gao, Bridgewater, NJ (US); Scott T. Harrison, Elkins Park, PA (US); Timothy J. Henderson, Natick, MA (US); Michael Man-Chu Lo, Bedminster, NJ (US); Robert D. Mazzola, Jr., Stewartsville, PA (US); Zhaoyang Meng, Ambler, PA (US); James Mulhearn, Elkins Park, PA (US); Vanessa L. Rada, Hatfield, PA (US); Jeffrey W. Schubert, North Wales, PA (US); Oleg B. Selyutin, West Windsor, NJ (US); David M. Tellers, Lansdale, PA (US); Ling Tong, Warren, NJ (US); Fengqi Zhang, Edison, NJ (US); Jianming Bao, South San Francisco, CA (US); and Chunsing Li, Shanghai (CN)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US); and MSD R&D (China) Co. LTD., Shanghai (CN)
Appl. No. 17/286,591
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US); and MSD R&D (China) Co. LTD., Shanghai (CN)
PCT Filed Oct. 24, 2019, PCT No. PCT/US2019/057746
§ 371(c)(1), (2) Date Apr. 19, 2021,
PCT Pub. No. WO2020/092102, PCT Pub. Date May 7, 2020.
Claims priority of application No. PCT/CN18/112403 (WO), filed on Oct. 29, 2018.
Prior Publication US 2021/0395224 A1, Dec. 23, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); C07D 405/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 405/14 (2013.01)] 18 Claims
 
1. A compound of the formula I:

OG Complex Work Unit Chemistry
wherein:
X is —N═ or —C(R8)═;
Y is —N═ or —C(R11)═;
R1 is selected from:
(1) hydrogen,
(2) halogen,
(3) —CN,
(4) —C1-6alkyl, which is unsubstituted or substituted with a hydroxy, pyrazolyl, dihydropyranyl, or 1-3 fluoro,
(5) —O—C1-6alkyl, which is unsubstituted or substituted with a hydroxy, or 1-3 fluoro,
(6) cyclopropyl,
(7) —C═CH2,
(8) —C≡CH,
(9) -pyrazolyl, which is unsubstituted or substituted with —C1-6alkyl, and
(10) dihydropyranyl;
R2 is selected from:
(1) hydrogen,
(2) halogen,
(3) —C1-6alkyl,
(4) —CN,
(5) —OC1-6alkyl, and
(6) —SC1-6alkyl;
R3 is selected from:
(1) hydrogen,
(2) chloro,
(3) —C1-6alkyl, and
(4) —OC1-6alkyl;
R4 is selected from:
(1) hydrogen, and
(2) fluoro;
R5 is —C1-6alkyl, which is unsubstituted or substituted with:
(1) fluoro,
(2) hydroxy,
(3) —CN,
(4) keto,
(5) —C1-6alkyl, which is unsubstituted or substituted with hydroxy, methoxy, fluoro, or —C1-6alkyl-fluoro,
(6) —C2-6alkenyl, which is unsubstituted or substituted with fluoro,
(7) —OC1-6alkyl, which is unsubstituted or substituted with —C1-6alkyl, hydroxy, methoxy, fluoro, or —C1-6alkyl-fluoro,
(8) —C3-4cycloalkyl or C6-10cycloalkyl, which is unsubstituted or substituted with —C1-6alkyl, hydroxy, methoxy, fluoro, or —C1-6alkyl-fluoro,
(9) tetrahydrofuranyl, which is unsubstituted or substituted with —C1-6alkyl, hydroxy, methoxy, or 1-3 fluoro,
(10) tetrahydropyranyl, which is unsubstituted or substituted with —C1-6alkyl, hydroxy, methoxy, or 1-3 fluoro, and
(11) phenyl, which is unsubstituted or substituted with —C1-6alkyl, hydroxy, methoxy, or 1-3 fluoro;
each of R8, R9, R10 and R11 is independently selected from:
(1) hydrogen,
(2) halogen,
(3) —C1-6alkyl, which is unsubstituted or substituted with: hydroxy, —OC1-6alkyl, cyclopropyl, cyclobutyl, or 1-3 fluoro; phenyl, which is unsubstituted or substituted with hydroxy, —C1-6alkyl or fluoro; or pyridyl, which is unsubstituted or substituted with hydroxy, —C1-6alkyl or fluoro,
(4) —OC1-6alkyl, which is unsubstituted or substituted with a hydroxy, —OC1-6alkyl, cyclopropyl, cyclobutyl, or 1-3 fluoro,
(5) —C3-6cyclolkyl, which is unsubstituted or substituted with a hydroxy, methoxy, or 1-3 fluoro, and
(6) —CN;
or a pharmaceutically acceptable salt thereof.