US 12,440,496 B2
Natriuretic peptide receptor a agonists useful for the treatment of cardiometabolic diseases, kidney disease and diabetes
Qingmei Hong, Scotch Plains, NJ (US); Jason E. Imbriglio, Bridgewater, NJ (US); Angela D. Kerekes, Plainfield, NJ (US); Tanweer Khan, Bridgewater, NJ (US); Claire Lankin, Highbridge, NJ (US); Derun Li, West Roxbury, MA (US); Rui Liang, East Brunswick, NJ (US); Pengcheng Patrick Shao, Fanwood, NJ (US); Zhicai Wu, Montvale, NJ (US); Yusheng Xiong, Plainsboro, NJ (US); Feng Ye, Scotch Plains, NJ (US); Hyewon Youm, Berkeley Heights, NJ (US); Yang Yu, Edison, NJ (US); Anthappan Tony Kurissery, Bangalore (IN); and Venukrishnan Komanduri, Manchester (GB)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/611,540
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US); and Changhong Shi, Scotch Plains, NJ (US)
PCT Filed May 18, 2020, PCT No. PCT/US2020/033354
§ 371(c)(1), (2) Date Nov. 15, 2021,
PCT Pub. No. WO2020/236688, PCT Pub. Date Nov. 26, 2020.
Claims priority of provisional application 62/851,539, filed on May 22, 2019.
Prior Publication US 2022/0273669 A1, Sep. 1, 2022
Int. Cl. C07D 495/04 (2006.01); A61K 31/438 (2006.01); A61K 31/444 (2006.01); A61K 31/4545 (2006.01); A61K 31/54 (2006.01); C07D 513/04 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/54 (2013.01) [A61K 31/438 (2013.01); A61K 31/444 (2013.01); A61K 31/4545 (2013.01); C07D 495/04 (2013.01); C07D 513/04 (2013.01); C07D 519/00 (2013.01)] 15 Claims
 
1. A compound of the formula I, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
X is N or CH;
R1 is selected from phenyl, pyridyl, thiazolyl, imidazolyl, pyrazinyl, and oxadiazolyl, wherein R1 is substituted by 0, 1, 2, or 3, R5;
R2 is independently selected from:
arylC0-10 alkyl,
C3-12 cycloalkylC0-10 alkyl,
heteroarylC0-10 alkyl,
heterocyclylC0-10 alkyl,
C1-10alkylaminoC0-10 alkyl,
heteroarylC0-10alkylaminoC0-10 alkyl,
heterocyclylC0-10alkylaminoC0-10 alkyl,
C1-10 heteroalkyl aminoC0-10 alkyl,
C3-12 cycloalkyl C0-10 alkylaminoC0-10 alkyl,
aryl C0-10 alkylaminoC0-10 alkyl,
amino, and
(C1-10 alkyl)1-2 amino;
wherein R2 is each substituted with 0, 1, 2, 3, or 4 R4 substituents;
each R3 is independently selected from hydrogen, halogen, C1-6alkyl, and C3-12 cycloalkyl C0-10 alkyl, and heterocyclylC0-10 alkyl, wherein R3 is substituted by 0, 1, 2 or 3 groups independently selected from C1-6 alkyl, C1-6 haloalkyl, and halogen;
each R4 is independently selected from:
halogen,
C1-10 alkyl,
C1-10 heteroalkyl,
aryl C0-10 alkyl,
C3-12 cycloalkyl C0-10 alkyl,
heteroaryl C0-10 alkyl,
heterocyclylC0-10 alkyl,
amino C0-10 alkyl,
((C1-10)alkyl)1-2amino,
—CO2 (C1-10 alkyl),
—(C0-10 alkyl) CO2H,
OXO,
hydroxy,
—(C1-10 alkyl)OH,
C1-10 alkoxy,
cyano, and
C1-6haloalkyl;
wherein R4 is each substituted with 0, 1, 2, 3, or 4 R8 substituents and each R8 is independently selected from: C1-10 alkyl, —CO2 (C1-10 alkyl), —(C0-10 alkyl) CO2H, C1-10 alkoxy, halogen, C1-6haloalkyl, cyano, oxo, hydroxy, and amino;
R5 is independently selected from:
halogen,
C1-10 alkyl,
aryl C0-10 alkyl,
C3-12 cycloalkylC0-10 alkyl,
heteroaryl C0-10 alkyl,
heterocyclyl C0-10 alkyl,
C1-10 alkylcarbonylC0-10 alkyl,
C1-10 heteroalkylcarbonylC0-10 alkyl,
arylcarbonylC0-10 alkyl,
(C3-12)cycloalkyl carbonylC0-10 alkyl,
heteroarylcarbonylC0-10 alkyl,
heterocyclylcarbonylC0-10 alkyl,
((C0-10)alkyl)1-2aminocarbonyl,
C1-10 alkoxy,
aryl C0-10 alkyloxy,
C3-12 cycloalkyloxy,
heteroaryl C0-10 alkyloxy,
heterocyclyl C0-10 alkyloxy,
(C0-10)alkylaminocarbonyl,
(C1-10)heteroalkylaminocarbonyl,
aryl(C0-10)alkylaminocarbonyl,
(C3-12)cycloalkyl(C0-10)alkylaminocarbonyl,
heteroaryl(C0-10)alkylaminocarbonyl,
heterocyclyl(C0-10)alkylaminocarbonyl,
C0-10 alkylcarbonylaminoC0-10 alkyl,
C1-10 heteroalkylcarbonylaminoC0-10 alkyl,
C3-12 cycloalkyl C0-10 alkylcarbonylaminoC0-10 alkyl,
aryl C0-10 alkylcarbonylaminoC0-10 alkyl,
heteroaryl C0-10 alkylcarbonylaminoC0-10 alkyl,
heterocyclyl C0-10 alkylcarbonylamino,
—SO2N(C1-6 alkyl)0-2,
C0-6 alkylS(O)1-2amino,
—SO2CF3,
—SO2CF2H,
amino,
(C0-10 alkyl)1-2 amino,
hydroxy,
(C1-10 alkyl)OH,
cyano,
C1-6haloalkyl,
—CO2 (C1-10 alkyl),
(C0-10 alkyl) CO2H,
OXO,
C1-10 alkylS(O)1-2,
C1-10 heteroalkyl S(O)1-2,
(C3-12)cycloalkylS(O)1-2,
heterocyclyl S(O)1-2,
heteroarylS(O)1-2, and
arylS(O)1-2;
wherein R5 is each substituted with 0, 1, 2, 3, or 4 R6;
each R6 is independently selected from:
halogen,
C1-10 alkyl,
C1-6 haloalkyl,
C1-10 heteroalkyl,
aryl C0-10 alkyl,
C3-12 cycloalkyl C0-10 alkyl,
heteroaryl C0-10 alkyl,
heterocyclyl C0-10 alkyl,
amino C0-10 alkyl,
((C1-10)alkyl)1-2amino,
—CO2 (C1-10 alkyl),
—(C0-10 alkyl) CO2H,
OXO,
hydroxy,
—(C1-10 alkyl)OH,
C1-10 alkoxy,
cyano, and
aminocarbonyl; and
wherein R6 is each substituted with 0, 1, 2, or 3, R7 substituents and each R7 is independently selected from: C1-4 alkyl, hydroxy, —CO2 (C1-6 alkyl), —(C0-6 alkyl) CO2H, C1-6 alkoxy, halogen, C1-6haloalkyl, cyano, and amino.