Patent ID: 8158659
Filing Date: 2012-04-17
Classification: A61K,A61P,C07D

Abstract:
1. A method for causing regression of, suppressing, or alleviating the symptoms of hypertension, comprising administering to a patient a therapeutically effective amount of a compound of formula II: wherein: r is 0, 1 or 2; Ar is selected from: R R 1a is H, —C 1-6 alkyl, —C 1-3 alkylenearyl, —C 1-3 alkyleneheteroaryl, —C 3-7 cycloalkyl, —CH(C 1-4 alkyl)OC(O)R 1aa , —C 0-6 alkylenemorpholine, R 1aa is —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —NR 1ab R 1ac , or —CH(NH 2 )CH 2 COOCH 3 ; R 1ab and R 1aa are independently selected from H, —C 1-6 alkyl, and benzyl, or are taken together as —(CH 2 ) 3-6 —; R 1b is R 1c or —NHC(O)R 1c ; R 1c is —C 1-6 alkyl, —C 0-6 alkylene- O—R 1ca , —C 1-5 alkylene-NR 1cb R 1cc , —C 0-4 alkylenearyl or —C 0-4 alkyleneheteroaryl; R 1ca is H, —C 1-6 alkyl, or —C 1-6 alkylene-O—C 1-6 alkyl; R 1cb and R 1cc are independently selected from H and —C 1-6 alkyl, or are taken together as —(CH 2 ) 2 —O—(CH 2 ) 2 — or —(CH 2 ) 2 —N[C(O)CH 3 ]—(CH 2 ) 2 —; R 1d is H, R 1c , —C(O)R 1c , or —C(O)NHR 1c ; R 1e is —C 1-4 alkyl or aryl; R R where R 1a is selected from H, —C 1-6 alkyl, —C 3-7 cycloalkyl, and —C 0-3 alkylenearyl; and R 3b is selected from H, —C 1-6 alkyl, —C 3-7 cycloalkyl, —C 2-4 alkenyl, —C 2-4 alkynyl, and aryl; X is —C R R 5ea is —O—C 1-6 alkyl, —O—C 3-7 cycloalkyl, —NR 5eb R 5ec , or —CH(NH 2 )CH 2 COOCH 3 ; R 5eb and R 5ec are independently selected from H, —C 1-4 alkyl, and —C 1-3 alkylenearyl, or are taken together as —(CH 2 ) 3-6 —; R 5f is H, —C 1-4 alkyl, —C 0-3 alkylenearyl, —C 1-3 alkylene-NR 5 fa R 5 fb , or —C 1-3 alkylene(aryl)—C 0-3 alkylene-NR 5fa R 5th ; R 5fa and R 5fb are independently selected from H and —C 1-4 alkyl; R 5g is H, —C 1-6 alkyl, —C 1-3 alkylenearyl, or —CH 2 —O—(CH 2 ) 2 —O—CH 3 ; R 5h is H or —C 1-4 alkyl; R 5i is H, —C 1-4 alkyl, or —C 0-3 alkylenearyl; and R 5j is —C 1-6 alkyl, aryl, or —CH 2 CH(NH 2 )COOH; R R wherein: each —CH 2 — group in —(CH 2 ) r — is optionally substituted with 1 or 2 substituents independently selected from —C 1-4 alkyl and fluoro; each ring in Ar and each aryl and heteroaryl in R 1-3 and R 5-6 is optionally substituted with 1 to 3 substituents independently selected from —OH, —C 1-6 alkyl, —C 2-4 alkenyl, —C 2-4 alkynyl, —CN, halo, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —S(O)—C 1-6 alkyl, —S(O) 2 —C 1-4 alkyl, phenyl, —NO 2 , —NH 2 , —NH—C 1-6 alkyl and —N(C 1-6 alkyl) 2 , wherein each alkyl, alkenyl and alkynyl is optionally substituted with 1 to 5 fluoro atoms; each carbon atom in X is optionally substituted with one or more R 4b groups and one —CH 2 — moiety in X may be replaced with a group selected from —C 4-8 cycloalkylene-, —CR 4d ═CH—, and —CH═CR 4d —; wherein R 4b is selected from —C 0-5 alkylene-COOR 4c , —C 1-6 alkyl, —C 0-1 alkylene-CONH 2 , —C 1-2 alkylene-OH, —C 0-3 alkylene-C 3-7 cycloalkyl, 1H-indol-3-yl, benzyl, and hydroxybenzyl, where R 4c is H or —C 1-4 alkyl; and R 4d is selected from —CH 2 -2-thiophene and phenyl; each alkyl and each aryl in R 1-3 , R 4a-4d , and R 5-6 is optionally substituted with 1 to 7 fluoro atoms; or a pharmaceutically acceptable salt thereof.