Claims
- 1. A compound of formula ##STR16## or a pharmaceutically acceptable acid addition or base salt thereof, wherein:
- one of X and X.sup.1 is nitrogen and the other is carbon;
- R and R.sup.1 are each independently
- hydrogen,
- halogen,
- lower alkyl,
- alkyl carboxylate,
- trihalomethyl,
- acetyl ester,
- cyano,
- cyanomethyl,
- acetamide,
- alkoxymethyl,
- hydroxymethyl,
- alkylthiomethyl,
- thiomethyl,
- COOH,
- CHO,
- 1-oxoalkyl,
- 2-oxoalkyl, or
- 3-oxoalkyl
- with the proviso that when X is nitrogen, R.sup.1 is absent,
- R.sup.2 is propyl,
- butyl,
- --CH.sub.2 CH.dbd.CH.sub.2,
- --CH.sub.2 CH.dbd.CH--CH.sub.3,
- --CH.sub.2 CH.sub.2 CH.dbd.CH.sub.2
- --CH.sub.2 C.tbd.CCH.sub.3,
- --CH.sub.2 CH.sub.2 C.tbd.CH,
- --SCH.sub.3,
- --SC.sub.2 H.sub.5,
- --SC.sub.3 H.sub.7,
- --SC.sub.4 H.sub.9,
- --OCH.sub.3,
- --OC.sub.2 H.sub.5,
- --OC.sub.3 H.sub.7,
- --OC.sub.4 H.sub.9,
- --SCH.sub.2 CH.dbd.CH.sub.2, or
- --OCH.sub.2 CH.dbd.CH.sub.2 ;
- and R.sub.3 is ##STR17## wherein R.sub.4 is ##STR18## R.sub.5 l is H,
- CH.sub.3,
- C.sub.2 H.sub.5,
- t-C.sub.4 H.sub.9,
- CH.sub.2 Ph;
- n is 0-3; and
- R.sub.6 is
- H,
- CH.sub.3,
- C.sub.2 H.sub.5,
- C.sub.3 H.sub.7,
- i--C.sub.3 H.sub.7,
- C.sub.4 H.sub.9,
- i--C.sub.4 H.sub.9,
- CH.sub.2 CH(CH.sub.3)CH.sub.2 CH.sub.3,
- CH.sub.2 CH.dbd.CH.sub.2,
- CH.sub.2 -cyclohexyl,
- CH.sub.2 --Ph, ##STR19##
- 2. A compound according to claim 1 wherein
- R and R.sup.1 are each independently,
- --CH.sub.2 OH,
- --CH.sub.2 SH,
- --CH.sub.2 OCH.sub.3,
- --CH.sub.2 SCH.sub.3,
- --CHO,
- --CO.sub.2 CH.sub.3,
- --C.tbd.N ##STR20## --CH.sub.2 C.sub.2 H.sub.5, --COOH,
- --CH.sub.3,
- --CH.sub.3,
- --H,
- --Cl,
- --Br,
- --F,
- --CH.sub.2 CO.sub.2 CH.sub.3,
- --CH.sub.2 CO.sub.2 C.sub.2 H.sub.5,
- --CH.sub.2 C.tbd.N,
- --CH.sub.2 CONH.sub.2,
- --CH.sub.2 CONHCH.sub.3, or
- --CH.sub.2 CON(CH.sub.3).sub.2
- with the proviso that when X is nitrogen, R.sup.1 is absent;
- R.sup.2 is
- propyl,
- butyl,
- thiomethyl,
- thioethyl,
- thiopropyl,
- thiobutyl,
- --CH.sub.2 CH.dbd.CH.sub.2,
- --CH.sub.2 CH.dbd.CH--CH.sub.3,
- --CH.sub.2 CH.sub.2 CH.dbd.CH.sub.2,
- --CH.sub.2 C.tbd.CCH.sub.3,
- --CH.sub.2 CH.sub.2 C.tbd.CH,
- --OCH.sub.3,
- --OCH.sub.2 H.sub.5,
- --OC.sub.3 H.sub.7,
- --OC.sub.4 H.sub.9,
- --SCH.sub.2 CH.dbd.CH.sub.2 or
- --OCH.sub.2 CH.dbd.CH.sub.2 ; and
- R.sub.3 is as above.
- 3. A compound according to claim 1 wherein
- X is carbon;
- X.sup.1 is nitrogen;
- R and R.sup.1 are each independently,
- --H,
- --CH.sub.2 OH,
- --CH.sub.2 OCH.sub.3,
- --CH.sub.2 CO.sub.2 CH.sub.3,
- --Cl,
- --Br, or
- --CF.sub.3
- with the proviso that when X is nitrogen R.sup.1 is absent;
- R.sub.2 is --C.sub.4 H.sub.9,
- --C.sub.3 H.sub.7,
- --SC.sub.2 H.sub.5, or
- --SC.sub.3 H.sub.7 ; and
- R.sub.3 is ##STR21## wherein R.sup.4 is
- CBZ,
- BOC,
- COPh,
- COCH.sub.3, ##STR22## SO.sub.2 Ph; n is 0-2;
- R.sup.5 is
- --H,
- --CH.sub.3,
- --CH.sub.2 H.sub.5,
- --t--C.sub.4 H.sub.9 or
- --CH.sub.2 Ph; and
- R.sup.6 is --CH.sub.3,
- --iC.sub.3 H.sub.7,
- --iC.sub.4 H.sub.9,
- --CH.sub.2 CH(CH.sub.3)CH.sub.2 CH.sub.3
- --CH.sub.2 Ph, ##STR23## --CH.sub.2 OH, --CH.sub.2 SH, or
- --CH(CH.sub.3)OH.
- 4. A compound selected from the list consisting of:
- (RS)-3-[[4-[[2-Butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]amino]-2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-oxopropanoic acid, ethyl ester;
- (RS)-3-[[4-[[2-Butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]amino]-2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-oxopropanoic acid;
- (RS)-3-[[4-[[2-Butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]amino-3-oxo-2-[[phenylmethoxy)carbonyl]amino]-propanoic acid, ethyl ester;
- (RS)-3-[[4-[[2-Butyl-4-chloro(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]amino]-3-oxo-2[[(phenylmethoxy)carbonyl]amino]-propanoic acid;
- (RS)-2-(acetylamino)3-[[4-[[2-butyl-4-chloro-5-(hydroxymethyl)-1-H-imidazol-1-yl]methyl]phenyl]amino]-3-oxo-propanoic acid, 1,1-dimethylethyl ester;
- (S)-N-[4-[[2-Butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]-2-[(4-morpholinylsulfonyl)amino]-3-phenylpropanamide; and
- (S)-2-(Benzenesulfonylamino)-N-[4-[[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]phenyl]-3-phenylpropanamide;
- 5. A pharmaceutical composition for treating hypertension associated with the renin angiotensin system in mammals comprising an antihypertensive amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier.
- 6. A method for treating hypertension in a mammal suffering therefrom comprising administering to said mammal an antihypertensive effective amount of a composition according to claim 5.
Parent Case Info
This application is a divisional of U.S. Ser. No. 07/529,071 filed May 25, 1990.
Foreign Referenced Citations (2)
Number |
Date |
Country |
253310 |
Jan 1988 |
EPX |
324377 |
Jul 1989 |
EPX |
Divisions (1)
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Number |
Date |
Country |
Parent |
529071 |
May 1990 |
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