Dual-acting antihypertensive agents

The compound of claim 30, wherein R1 is —C1-6alkylene-OH, —COOH, —CHO, —C1-3alkylene-NHCH(COOH)(C1-6alkyl), or —C(O)NHCH2R1b;

• where R1b is —C0-3alkylenearyl or —C0-3alkyleneheteroaryl;
• R2 is H or halo;
• R3 is —C1-10alkyl;
• X is —SO2NHC(O)— or —SO2NHC(O)—C1-9alkylene-NHC(O)—;
• R6 is —C1-6alkyl or —C0-3alkylenearyl;
• and R7 is H or is taken together with R6 to form —C3-8cycloalkyl;
• where one —CH2— in the —C1-9alkylene-portion of X is optionally replaced with —C4-8cycloalkylene-;
• one —CH2— moiety is optionally replaced with a —NHC(O)— moiety;
• one —CH2— moiety is optionally substituted with —COOH;
• and the aryl in R6 is optionally substituted with phenyl.

A compound of formula II, and salts thereof:

• where
• Y is:
• Q is —C(R3)—, Z is a bond, and W is —N—;
• or
• Y is:
• Q is —C(R3)—, Z is —C(O)—, and W is —N—;
• R1 is selected from —C1-6alkylene-OH, —COOR1a, —CHO, —C1-3alkylene-NHCH(COOH)(C1-6alkyl), —C(O)NHCH(COOH)(C1-6alkyl), and —C(O)NHCH2R1b;
• where R1a is H or —C1-6alkyl;
• and R1b is —C0-3alkylenearyl or —C0-3alkyleneheteroaryl;
• R2 is selected from H, —CH2OH, halo, —NO2, —C1-6alkyl, —C2-6alkenyl, —C3-6cycloalkyl, —CN, —C(O)R2a, and —C0-3alkylenearyl;
• where R2a is H, —C1-6alkyl, —C3-6cycloalkyl, —C0-3alkylene-phenyl, —OR2b, or —NR2cR2d;
• R2b is H, —C1-6alkyl, —C3-6cycloalkyl, phenyl, or benzyl;
• and R2c and R2d are independently H, —C1-4alkyl, or —C0-1alkylene-phenyl;
• R3 is selected from —C1-10alkyl, —C2-10alkenyl, —C3-10alkynyl, —C0-3alkylene-C3-7cycloalkyl, —C2-3alkenylene-C3-7cycloalkyl, —C2-3alkynylene-C3-7cycloalkyl, —C0-5alkylene-NR3a—C0-5alkylene-R3b—C0-5alkylene-O—C0-5alkylene-R3b, —C0-5alkylene-S—C1-5alkylene-R3b, and —C0-3alkylenearyl;
• R3a is H, —C1-6alkyl, —C3-7cycloalkyl, or —C0-3alkylenearyl;
• and R3b is H, —C1-6alkyl, —C3-7cycloalkyl, —C2-4alkenyl, —C2-4alkynyl, or aryl;
• r is 1.
• Ar—X—CR5*R6R7 is selected from:
• X is selected from —SO2NHC(O)—, —SO2NHC(O)—C1-12alkylene-NHC(O)—, —SO2NHC(O)—C1-12alkylene-C(O)NH—, —C(O)NH—SO2—C1-12alkylene-NHC(O)—, —C(O)NH—SO2—C1-12alkylene-C(O)NH—, —SO2NHC(O)NH—C2-12alkylene-NHC(O)—, —SO2NHC(O)NH—C1-12alkylene-C(O)NH—, —NH—SO7—NHC(O)—C1-12alkylene-NHC(O)—, and —NH—SO2—NHC(O)—C1-12alkylene-C(O)NH—;
• R5* is selected from —C0-3alkylene-S—P3, —C0-3alkylene-C(O)NH(O—P5), —C0-3alkylene-N(O—P5)—C(O)R5d, —C0-1alkylene-NHC(O)CH2S—P3, —NH—C0-1alkylene-P(O)(O—P7)2, —C0-3alkylene-P(O)(O—P7)—R5e, —C0-2alkylene-CHR5f—C(O)O—P2 and —C0-3alkylene-C(O)NR5g—CHR5h—C(O)O—P2;
• R5d is H, —C1-4alkyl, —C0-3alkylenearyl, —NR5daR5db, —CH2SH, or —O—C1-6alkyl;
• R5da and R5db are independently H or —C1-4alkyl;
• R5e is H, —C1-6alkyl, —C1-3alkylenearyl, —C1-3alkyleneheteroaryl, —C3-7cycloalkyl, —CH(CH3)—O—C(O)R5ea,
• R5ea is —O—C1-6alkyl, —O—C3-7cycloalkyl, —NR5ebR5ec or —CH(NH2)CH2COOCH3;
• R5eb and R5ec are independently H, —C1-4alkyl, or —C1-3alkylenearyl, or are taken together as —(CH2)3-6—;
• R5f is H, —C1-4alkyl, —C0-3alkylenearyl, —C1-3alkylene-NR5faR5th, or
• C1-3alkylene(aryl)-C0-3alkylene-NR5faR5th;
• R5fa and R5fb are independently H or —C1-5alkyl;
• R5g is H, —C1-6alkyl, —C1-3alkylenearyl, or —CH2—O—(CH2)2—OCH1;
• R5h is H or —C1-4alkyl;
• R6 is selected from —C1-6alkyl, —CH2—O—(CH2)2—OCH3, —C1-6alkylene-O—C1-6alkyl, —C0-3alkylenearyl, —C0-3alkyleneheteroaryl, and —C0-3alkylene-C3-7cycloalkyl;
• and
• R7 is H or is taken together with R6 to form —C3-8cycloalkyl;
• one —CH2— in the —C1-12alkylene-portion of X is optionally replaced with —C4-8cycloalkylene- or phenylene;
• one or more —CH2— moieties are optionally replaced with a —NR4—C(O)— or —C(O)—NR4— moiety, where R4 is H, —OH, or —C1-4alkyl;
• and one or more —CH2-moieties are optionally substituted with —COOH or an amino acid side chain;
• each alkyl and each aryl in R1-6 is optionally substituted with 1 to 7 fluoro atoms;
• each ring in Ar—X—CR5*R6R7 and each aryl and heteroaryl in R1, R2, R3, and R5-6 is optionally substituted with 1 to 3 substituents independently selected from —OH, —C1-6alkyl, —C2-4 alkenyl, —C2-4 alkynyl, —CN, halo, —O—C1-6 alkyl, —S—C1-6 alkyl, —S(O)—C1-6 alkyl, —S(O)2—C1-4alkyl, phenyl, —NO2—NH2—NH—C1-6alkyl and —N(C1-6alkyl)7, wherein each alkyl, alkenyl and alkynyl is optionally substituted with 1 to 5 fluoro atoms;
• and
• P2 is a carboxy-protecting group, P3 is a thiol-protecting group, P5 is a hydroxyl-protecting group, and P7 is a phosphate-protecting group.