Natriuretic peptide receptor a agonists useful for the treatment of cardiometabolic diseases, kidney disease and diabetes

A compound of the formula I, or a pharmaceutically acceptable salt thereof:

• 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.