| 摘要 |
In one aspect, the invention relates to compounds having the formula:;;where R1-R6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds. |
| 主权项 |
1. A compound of formula I:where:
R1 is selected from H, —C1-8alkyl, C1-6 alkylene-OC(O)R10, andwhere R10 is C1-6alkyl, —O—C1-6alkyl, or —CH(R15)—NHC(O)O—C1-6alkyl, R14 is —C1-6alkyl; R15 is —CH(CH3)2;
R2 is —OR21 or —CH2OR21; and R3 is H or —CH3; where R21 is H, —C(O)—C1-6alkyl, —C(O)—CH(R22)—NH2, —C(O)—CH(R22)—NHC(O)O—C1-6alkyl, or —P(O)(OR23)2; R22 is H, —CH3, —CH(CH3)25 phenyl, or benzyl; R23 is H, —C1-6alkyl, or phenyl; Z is selected from —CH— and —N—; R4 is selected from H, —C1-8alkyl, —C1-3alkylene-O—C1-8 alkyl, —C1-3alkylene-O—C6-10aryl, [(CH2)2O]1-3 CH3, andwhere R44 is —C1-6alkyl
a is 0 or 1; R5 is selected from halo, —CH3, —CF3, and —CN; b is 0 or an integer from 1 to 3; each R6 is independently selected from halo, —OH, —CH3, —OCH3, —CN, and —CF3; where each alkyl group in R1 and R4 is optionally substituted with 1 to 8 fluoro atoms; and where the methylene linker on the biphenyl is optionally substituted with one or two —C1-6alkyl groups or cyclopropyl; or a pharmaceutically acceptable salt thereof. |
