Soluble guanylate cyclase activators
AssigneeMerck Sharp & Dohme Corp.
InventorsRonald M. Kim, Emma R. Parmee, Christopher Joseph Sinz, Olga A. Ziouzina
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Abstract
This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.
Claims23
A compound of structural Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- W is selected from the group consisting of CH and N;
- Z is selected from the group consisting of:
- R1 is selected from the group consisting of —OH, —OC1-6 alkyl and —N(R5)2;
- R2 is selected from the group consisting of —C1-2 perfluoroalkyl and —NH2;
- R3 is selected from the group consisting of:
- 1) —C1-6 alkyl substituted with 1-3 of —F,
- 2) —COR4 and
- 3) —SO2R6;
- R3a is selected from the group consisting of —H;
- —C1-3 alkyl;
- C3-6 cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F;
- and —CH2—C3-6cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F;
- R4 is selected from the group consisting of:
- 1) —H,
- 2) —C1-3 alkyl,
- 3) —OC1-3 alkyl
- 4) —C3-6 cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F,
- 5) —CH2—C3-6cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F,
- 6) —OC3-6 cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F, and
- 7) —N(R5)2;
- R5 is independently selected at each occurrence from —H and —C1-3 alkyl;
- R6 is selected from the group consisting of —C1-3alkyl;
- —C3-6cycloalkyl optionally mono- or di- substituted with one or more substituents selected from the group consisting of —CH3 and —F;
- and —CH2—C3-6cycloalkyl optionally mono- or di-substituted with one or more substituents selected from the group consisting of —CH3 and —F;
- R7 is selected from the group consisting of —H and —CH3;
- Ra and Rb are independently selected at each occurrence from —F, —Cl and —Cl1-3 alkyl optionally substituted with 1-3 of —F;
- and
- Rc and Rd are independently selected at each occurrence from —F, —Cl and —C1-3 alkyl optionally substituted with 1-3 of —F.
Dependencies are inferred from the claim text.