| 摘要 |
The present invention provides compounds of Formula I;;and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention. |
| 主权项 |
1. A compound having structural Formula Ior a pharmaceutically acceptable salts thereof wherein:
R1 is —H or —C1-4alkyl; X is O, NH or S; Z1 is R2 is —H, halo, —C1-6alkyl, —C3-6cycloalkyl or —OC1-6alkyl; R3 is —H, halo, —CN, —C1-6alkyl, —C3-6cycloalkyl, —OC1-6alkyl or N-tetrazolyl optionally substituted with —CH3; R4 is —H, halo, —CN, —C1-6alkyl, —C3-6cycloalkyl, —OC1-6alkyl or N-tetrazolyl optionally substituted with —CH3;or R3 and R4 are joined together, and with the phenyl ring to which they are attached together represent:wherein R is —H or —C1-4alkyl;
R5 is —H, halo, —CN, —C1-4alkyl, —OC1-4alkyl or —C3-6cycloalkyl; provided that when R3 and R4 are not joined together, then
(a) one and only one of R3, R4 or R5 is —CN, or(b) one of R3 or R4 is N-tetrazolyl optionally substituted with —CH3 and the other is not N-tetrazolyl optionally substituted with —CH3; Z2 is R2a is —H, halo, —C1-6alkyl, —C3-6cycloalkyl or —OC1-6alkyl; R3a is —H, halo, —CN, —C1-6alkyl, —C3-6cycloalkyl, —OC1-6alkyl or N-tetrazolyl optionally substituted with —CH3; R4a is —H, halo, —CN, —C1-6alkyl, —C3-6cycloalkyl, —OC1-6alkyl or N-tetrazolyl optionally substituted with —CH3;or R3a and R4a are joined together, and with the phenyl ring to which they are attached together represent:wherein Ra is —H or —C1-4alkyl;
R5a is —H, halo, —CN, —C1-4alkyl, —OC1-4alkyl or —C3-6cycloalkyl; provided that when R3a and R4a are not joined together, then
(a) one of R3a, R4a or R5a is —CN and the others are not —CN, or(b) one of R3a or R4a is N-tetrazolyl optionally substituted with —CH3 and the other is not N-tetrazolyl optionally substituted with —CH3; R6 is —H, —OH or —C1-3alkyl; or R6 is —O— and is joined together with Z2 to represent: R7 is —H; or R7 together with —CHR6— and Z2 represents R8 is —H or —C1-3alkyl; and R9 is —H or —CH3. |
