Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents

A compound of formula I:

• where:
• Z represents a thiazole selected from:
• Ar is selected from:
• R1 is selected from —SO2NHC(O)R1a, tetrazolyl, —COOR1b,
• where R1a is —C1-6alkyl, —C0-6alkylene-OR1b, —C3-7cycloalkyl, —C0-5alkylene-NR1bR1b, pyridyl, isoxazolyl, methylisoxazolyl, pyrrolidinyl, morpholinyl, or phenyl optionally substituted with halo;
• where each R1b is independently selected from H and —C1-6alkyl;
• a is 0, 1, or 2;
• R2 is F;
• R3 is selected from —C2-5alkyl and —O—C1-5alkyl;
• R4 is selected from —CH2—SR4a, —CH2—N(OH)C(O)H, —CH(R4b)C(O)NH(OR4d), and —CH(R4b)COOR4c;
• where R4a is H or —C(O)—C1-6alkyl;
• R4b is H or —OH;
• and R4c is H, —C1-6alkyl, —C0-6alkylenemorpholine, —CH2OC(O)O—C1-6alkyl, —CH(CH3)OC(O)O—C1-6alkyl, —CH(CH3)OC(O)O—C3-7cycloalkyl, or:
• R4d is H or —C(O)—R4e;
• and R4e is —C1-6alkyl, —C1-6alkyl-NH2 or aryl;
• and
• R5 is selected from —C1-6alkyl, —CH2-furanyl, —CH2-thiophenyl, benzyl, and benzyl substituted with one or more halo, —CH3, or —CF3 groups;
• where each ring in Ar is optionally substituted with 1 to 3 substituents independently selected from —OH, —C1-6alkyl, —C2-4alkenyl, —C2-4alkynyl, —CN, halo, —O—C1-6alkyl, —S—C1-6alkyl, —S(O)—C1-6alkyl, —S(O)2—C1-4alkyl, phenyl, —NO2, —NH2, —NH—C1-6alkyl and —N(C1-6alkyl)2, wherein each alkyl, alkenyl and alkynyl is optionally substituted with 1 to 5 fluoro atoms;
• or a pharmaceutically acceptable salt thereof.