Claims
- 1. A compound having the formula: ##STR55## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is (a) --COOH,
- (b) --SO.sub.2 NH-heteroaryl as defined below,
- (c) --CH.sub.2 SO.sub.2 NH-heteroaryl as defined below,
- (d) --SO.sub.2 NH--CO--R.sup.21,
- (e) --CH.sub.2 SO.sub.2 NH--CO--R.sup.21,
- (f) --CONH--SO.sub.2 R.sup.21,
- (g) --CH.sub.2 CONH--SO.sub.2 R.sup.21,
- (h) --NHSO.sub.2 NHCO--R.sup.21,
- (i) --NHCONHSO.sub.2 R.sup.21,
- (j) --SO.sub.2 NHCONHR.sup.21, ##STR56## wherein: heteroaryl is an unsubstituted, monosubstituted or disubstituted five-membered aromatic ring which can contain from 1 to 3 nitrogen atoms and wherein the substituents are members selected from the group consisting of --OH, --SH, --C.sub.1 -C.sub.4 -alkyl, --C.sub.1 -C.sub.4 -alkoxy, --CF.sub.3, halo(Cl, Br, F, I), --NO.sub.2, --CO.sub.2 H, --CO.sub.2 -C.sub.1 -C.sub.4 -alkyl, --NH.sub.2, NH(C.sub.1 -C.sub.4 -alkyl) and --N(C.sub.1 -C.sub.4 -alkyl).sub.2 ;
- R.sup.2a is H;
- R.sup.2b is H, Cl, C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -alkoxy;
- R.sup.3a is H,
- R.sup.3b is
- (a) H,
- (b) Cl,
- (c) C.sub.1 -C.sub.4 -alkyl,
- (d) C.sub.5 -C.sub.6 -cycloalkyl, or
- (e) C.sub.1 -C.sub.4 -alkoxy;
- wherein aryl is phenyl or naphthyl optionally substituted with one or two substituents selected from V and W as defined below;
- R.sup.4 is H or C.sub.1 -C.sub.4 -alkyl;
- E is a single bond;
- R.sup.6 is C.sub.1 -C.sub.5 -alkyl;
- A--B--C together are:
- (a) --C(R.sup.7a).dbd.C(R.sup.7b)--Y--,
- (b) --Y--C(R.sup.7a).dbd.C(R.sup.7b)--;
- Y is S; R.sup.7a and R.sup.7b are independently:
- (a) H;
- (b) straight chain or branched C.sub.1 -C.sub.6 -alkyl, which is optionally substituted with OH, CO.sub.2 R.sup.4, N(R.sup.4).sub.2 or CON(R.sup.4).sub.2 ;
- (c) aryl or aryl-C.sub.1 -C.sub.4 -alkyl wherein the aryl can be optionally substituted with H, halo, C.sub.1 -C.sub.4 -alkyl, hydroxy-C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy or CO.sub.2 R.sup.4 ;
- (d) CO.sub.2 R.sup.4 ;
- (e) CON(R.sup.4).sub.2 ;
- (f) halo (Cl, Br, F, I);
- R.sup.21 is
- (a) aryl as defined above,
- (b) heteroaryl as defined above,
- (c) C.sub.3 -C.sub.7 -cycloalkyl;
- X is:
- (a) a single bond,
- (b) --CO--,
- (c) --O--,
- (d) --S--, ##STR57## (h) --OCH.sub.2, (i) --CH.sub.2 O--,
- (j) --SCH.sub.2 --,
- (k) --CH.sub.2 S--,
- (l) --NHC(R.sup.9)(R.sup.10)--,
- (m) NR.sup.9 SO.sub.2 --,
- (n) --SO.sub.2 NR.sup.9 --,
- (o) --C(R.sup.9)(R.sup.10)NH--,
- (p) --CH.dbd.CH--,
- (q) --CF.dbd.CF--,
- (r) --CH.dbd.CF--,
- (s) --CF.dbd.CH--,
- (t) --CH.sub.2 CH.sub.2 --,
- (u) --CF.sub.2 CF.sub.2 --, ##STR58## Z is NR.sup.13 ; and r is 1 or 2.
- 2. The compound of claim 1 which is a member of the group:
- (1) 6-methyl-2-propyl-3-[(2'-{1H-tetrazol-5-yl}-{1,1'-biphenyl}-4-yl)methyl]-3H-thieno[2,3-d]imidazole-5-methanol;
- (2) 2-butyl-6-methyl-3-[(2'-{1H-tetrazol-5-yl}{1,1'-biphenyl}-4-yl)methyl]-3H-thieno[2,3-d]imidazole-5-carboxylic acid;
- (3) 2-butyl-1-[(2'-{1H-tetrazol-5-yl}{1,1'-biphenyl}-4-yl)methyl]-1H-thieno[2,3-d]imidazole-5-carboxylic acid methyl ester;
- (4) 2-butyl-3-[(2'-carboxy{1,1'-biphenyl}-4-yl)-methyl]-3H-thieno[2,3-d]imidazole-5-carboxylic acid methyl ester;
- (5) 2-butyl-3-[(2'-{1H-tetrazol-5-yl}{1,1'-biphenyl}-4-yl)methyl]-3H-thieno[2,3-d]imidazole-5-carboxylic acid methyl ester;
- (6) 2-butyl-1-[(2'-{1H-tetrazol-5-yl}{1,1'-biphenyl}-4-yl)methyl]-1H-thieno[2,3-d]imidazole-5-carboxylic acid methyl ester; and,
- (7) 2-butyl-1-[(2'-{(N-phenlsulfonyl)carboxamido}{1,1'-biphen}-4-yl)methyl]-1H-thieno[2,3-d]-imidazole-5-carboxylic acid methyl ester.
- 3. A pharmaceutical composition useful in the treatment of hypertension which comprises a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1.
- 4. A method of treating hypertension which comprises administering to a patient in need of such treatment a pharmaceutically effective amount of a compound of claim 1.
INTRODUCTION OF THE INVENTION
This is a continuation-in-part of copending application Ser. No. 375,655 filed Jul. 3, 1989, abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4880804 |
Carini et al. |
Nov 1989 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
245637 |
Nov 1987 |
EPX |
399731 |
Nov 1990 |
EPX |
Non-Patent Literature Citations (2)
Entry |
Chiu et al., Eur. J. Pharm. Exp. Ther. 157, 13-21 (1988). |
Wong et al., J. Pharm. Exp. Ther. 247, 1-7 (1988). |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
375655 |
Jul 1989 |
|