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Claims for Patent: 5,138,069

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Claims for Patent: 5,138,069

Title: Angiotensin II receptor blocking imidazoles
Abstract:Substituted imidazoles such as ##STR1## are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.
Inventor(s): Carini; David J. (Wilmington, DE), Duncia; John J. V. (Newark, DE), Wong; Pancras C. B. (Wilmington, DE)
Assignee: E. I. Du Pont de Nemours and Company (Wilmington, DE)
Application Number:07/279,194
Patent Claims: 1. An antihypertensive compound of the formula: ##STR487## wherein R.sup.1 is ##STR488## R.sup.2 is H; Cl; Br; I; F; NO.sub.2 ; CN; alkyl of 1 to 4 carbon atoms; acyloxy of 1 to 4 carbon atoms; alkoxy of 1 to 4 carbon atoms; CO.sub.2 H; CO.sub.2 R.sup.9 ; NHSO.sub.2 CH.sub.3 ; NHSO.sub.2 CF.sub.3 ; ##STR489## R.sup.3 is H; Cl, Br, I or F; alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms;

R.sup.4 is CN, NO.sub.2 or CO.sub.2 R.sup.11 ;

R.sup.5 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms alkenyl or alkynyl of 2 to 4 carbon atoms;

R.sup.6 is alkyl of 2 to 10 carbon atoms, alkenyl or alkynyl of 3 to 10 carbon atoms or the same groups substituted with F or CO.sub.2 R.sup.14 ; cycloalkyl of 3 to 8 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms; cycloalkylalkenyl or cycloalkylalkynyl of 5 to 10 carbon atoms; (CH.sub.2).sub.s Z(CH.sub.2).sub.m R.sup.5 optionally substituted with F or CO.sub.2 R.sup.14 ; benzyl or benzyl substituted on the phenyl ring with 1 or 2 halogens, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or nitro;

R.sup.7 is H, F, Cl, Br, I, NO.sub.2, C.sub.v F.sub.2v+1, where v=1-6, C.sub.6 F.sub.5 ; CN; ##STR490## straight or branched alkyl of 1 to 6 carbon atoms; phenyl or phenylalkyl, where alkyl is 1 to 3 carbon atoms; or substituted phenyl or substituted phenylalkyl, where alkyl is 1 to 3 carbon atoms, substituted with one or two substituents selected from alkyl of 1 to 4 carbon atoms, F, Cl, Br, OH, OCH.sub.3, CF.sub.3, and COOR, where R is H, alkyl of 1 to 4 carbon atoms, or phenyl;

R.sup.8 is H, CN, alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, or the same groups substituted with F; phenylalkenyl wherein the alkenyl portion is 2 to 6 carbon atoms; --(CH.sub.2).sub.m -imidazol-1-yl; --(CH.sub.2).sub.m -1,2,3-triazolyl optionally substituted with one or two groups selected from CO.sub.2 CH.sub.3 or alkyl of 1 to 4 carbon atoms; --(CH.sub.2).sub.s -tetrasolyl; ##STR491## R.sup.9 is ##STR492## R.sup.10 is alkyl of 1 to 6 carbon atoms or perfluoroalkyl of 1 to 6 carbon atoms, 1-adamantyl, 1-naphthyl, 1-(1-naphthyl)ethyl, or (CH.sub.2).sub.p C.sub.6 H.sub.5 ;

R.sup.11 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl or benzyl;

R.sup.12 is H, methyl or benzyl;

R.sup.13 is --CO.sub.2 H; --CO.sub.2 R.sup.9 ; --CH.sub.2 CO.sub.2 H, --CH.sub.2 CO.sub.2 R.sup.9 ; ##STR493## R.sup.14 is H, alkyl or perfluoroalkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl or benzyl;

R.sup.15 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl, benzyl, acyl of 1 to 4 carbon atoms, phenacyl;

R.sup.16 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, (CH.sub.2).sub.p C.sub.6 H.sub.5, OR.sup.17, or NR.sup.18 R.sup.19 ;

R.sup.17 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, phenyl or benzyl;

R.sup.18 and R.sup.19 independently are H, alkyl of 1 to 4 carbon atoms, phenyl, benzyl, .alpha.-methylbenzyl, or taken together with the nitrogen form a ring of the formula ##STR494## Q is NR.sup.20, O or CH.sub.2 ; R.sup.20 is H, alkyl of 1-4 carbon atoms, or phenyl;

R.sup.21 is alkyl of 1 to 6 carbon atoms, --NR.sup.22 R.sup.23, ##STR495## R.sup.22 and R.sup.23 independently are H, alkyl of 1 to 6 carbon atoms, benzyl, or are taken together as (CH.sub.2).sub.u where u is 3-6;

R.sup.24 is H, CH.sub.3 or --C.sub.6 H.sub.5 ;

R.sup.25 is NR.sup.27 R.sup.28, OR.sup.28, NHCONH.sub.2, NHCSNH.sub.2, ##STR496## R.sup.26 is hydrogen, alkyl with from 1 to 6 carbon atoms, benzyl, or allyl;

R.sup.27 and R.sup.28 are independently hydrogen, alkyl with from 1 to 5 carbon atoms, or phenyl;

R.sup.29 and R.sup.30 are independently alkyl of 1-4 carbon atoms or taken together are --(CH.sub.2).sub.q --;

R.sup.31 is H, alkyl of 1 to 4 carbon atoms, --CH.sub.2 CH.dbd.CH.sub.2 or --CH.sub.2 C.sub.6 H.sub.4 R.sup.32 ;

R.sup.32 is H, NO.sub.2, NH.sub.2, OH or OCH.sub.3 ;

X is a carbon--carbon single bond, --CO--, --CH.sub.2 --, --O--, --S--, ##STR497## Y is O or S; Z is O, NR.sup.11, or S;

m is 1 to 5;

n is 1 to 10;

p is 0 to 3;

q is 2 to 3;

r is 0 to 2;

s is 0 to 5;

t is 0 or 1;

and pharmaceutically acceptable salts of these compounds;

provided that:

(1) the R.sup.1 group is not in the ortho position;

(2) when R.sup.1 is ##STR498## X is a single bond, and R.sup.13 is CO.sub.2 H, or ##STR499## then R.sup.13 must be in the ortho or meta position; or when R.sup.1 and X are as above and R.sup.13 is NHSO.sub.2 CF.sub.3 or NHSO.sub.2 CH.sub.3, R.sup.13 must be ortho;

(3) when R.sup.1 is ##STR500## and X is other than a single bond, then R.sup.13 must be ortho except when X=NR.sup.23 CO and R.sup.13 is NHSO.sub.2 CF.sub.3 or NHSO.sub.2 CH.sub.3, then R.sup.13 must be ortho or meta;

(4) when R.sup.1 is 4--CO.sub.2 H or a salt thereof, R.sup.6 cannot be S-alkyl;

(5) when R.sup.1 is 4--CO.sub.2 H or a salt thereof, the substituent on the 4-position of the imidazole cannot be CH.sub.2 OH, CH.sub.2 OCOCH.sub.3, or CH.sub.2 CO.sub.2 H;

(6) when R.sup.1 is ##STR501## X is --OCH.sub.2 --, and R.sup.13 is 2--CO.sub.2 H, and R.sup.7 is H then R.sup.6 is not C.sub.2 H.sub.5 S;

(7) when R.sup.1 is ##STR502## and R.sup.6 is n-hexyl then R.sup.7 and R.sup.8 are not both hydrogen; (8) when R.sup.1 is ##STR503## R.sup.6 is not methoxybenzyl; (9) the R.sup.6 group is not ##STR504## (10) when r=0, R.sup.1 is ##STR505## X is ##STR506## R.sup.13 is 2-NHSO.sub.2 CF.sub.3, and R.sup.6 is n-propyl, then R.sup.7 and R.sup.8 are not --CO.sub.2 CH.sub.3 ;

(11) when r=0, R.sup.1 is ##STR507## X is ##STR508## R.sup.13 is 2--COOH, and R.sup.6 is n-propyl, then R.sup.7 and R.sup.8 are not --CO.sub.2 CH.sub.3 ;

(12) when r=1, R.sup.1 = ##STR509## X is a single bond, R.sup.7 is Cl, and R.sup.8 is --CHO, then R.sup.13 is not 3-(tetrasol-5-yl);

(13) when r=1, R.sup.1 = ##STR510## X is a single bond, R.sup.7 is Cl, and R.sup.8 is --CHO, then R.sup.13 is not 4-(tetrasol-5-yl);

(14) when r=0, then R.sup.1 is not 4-NHSO.sub.2 CH.sub.3 or 4-NHSO.sub.2 CF.sub.3.

2. A compound of claim 1 having the formula: ##STR511## wherein R.sup.1 is --CO.sub.2 H; --NHSO.sub.2 CF.sub.3 ; ##STR512## R.sup.6 is alkyl of 3 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, alkynyl of 3 to 10 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, benzyl substituted on the phenyl ring with up to two groups selected from alkoxy of 1 to 4 carbon atoms, halogen, alkyl of 1 to 4 carbon atoms, and nitro;

R.sup.8 is phenylalkenyl wherein the aliphatic portion is 2 to 4 carbon atoms, --(CH.sub.2).sub.m -imidazol-l-yl, --(CH.sub.2).sub.m -1,2,3-triazolyl optionally substituted with one or two groups selected from CO.sub.2 CH.sub.3 or alkyl of 1 to 4 carbon atoms, ##STR513## R.sup.13 is --CO.sub.2 H, --CO.sub.2 R.sup.9, NHSO.sub.2 CF.sub.3 ; SO.sub.3 H; or ##STR514## R.sup.16 is H, alkyl of 1 to 5 carbon atoms, OR.sup.17, or NR.sup.18 R.sup.19 ;

X is carbon-carbon single bond, --CO--, ##STR515## pharmaceutically acceptable salts of these compounds.

3. A compound of claim 2 wherein:

R.sup.2 is H, alkyl of 1 to 4 carbon atoms, halogen, or alkoxy of 1 to 4 carbon atoms;

R.sup.6 is alkyl, alkenyl or alkynyl of 3 to 7 carbon atoms;

R.sup.7 is H, Cl, Br, I; C.sub.v F.sub.2v+1, where v=1-3; or ##STR516## R.sup.8 is ##STR517## R.sup.10 is CF.sub.3, alkyl of 1 to 6 carbon atoms or phenyl; R.sup.11 is H, or alkyl of 1 to 4 carbon atoms;

R.sup.13 is CO.sub.2 H; CO.sub.2 CH.sub.2 OCOC(CH.sub.3).sub.3 ; NHSO.sub.2 CF.sub.3 ##STR518## R.sup.14 is H, or alkyl of 1 to 4 carbon atoms; R.sup.15 is H, alkyl of 1 to 4 carbon atoms, or acyl of 1 to 4 carbon atoms;

R.sup.16 is H, alkyl of 1 to 5 carbon atoms; OR.sup.17 ; or ##STR519## m is 1 to 5; X=single bond, --O--; --CO--; --NHCO--; or --OCH.sub.2 --; and

pharmaceutically acceptable salts.

4. A compound of claim 3 wherein R.sup.1 is ##STR520## and X is a single bond, and pharmaceutically suitable salts thereof.

5. The compound of claim 4, 2-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxy methyl)imidazole, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 4, 2-Butyl-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]-5-(hydroxymethyl)-imi dazole, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 4, 2-Butyl-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]-5-[(methoxycarbonyl)- aminomethyl]imidazole, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 4, 2-Butyl-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]-5-[(propoxycarbonyl)- aminomethyl]imidazole, or a pharmaceutically acceptable salt thereof.

9. The compound of claim 4, 2-Butyl-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]imidazole-5-carboxalde hyde, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 4, 2-Butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde, or a pharmaceutically acceptable salt thereof.

11. The compound of claim 4, 2-(1E-Butenyl)-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]-5-(hydroxymeth yl)imidazole, or a pharmaceutically acceptable salt thereof.

12. The compound of claim 4, 2-(1E-Butenyl)-4-chloro-1-[(2'-carboxybiphenyl-4-yl)methyl]imidazole-5-car boxaldehyde, or a pharmaceutically acceptable salt thereof.

13. The compound of claim 4, 2-propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methl]-5-(hydroxy methyl)imidazole, or a pharmaceutically acceptable salt thereof.

14. The compound of claim 4, 2-propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole- 5-carboxaldehyde, or a pharmaceutically acceptable salt thereof.

15. The compound of claim 4, 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)imidazole-5 -carboxaldehyde, or a pharmaceutically acceptable salt thereof.

16. The compound of claim 4, 2-(1E-butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-h ydroxymethyl)imidazole, or a pharmaceutically acceptable salt thereof.

17. The compound of claim 4, 2-(1E-butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imi dazole-5-carboxaldehyde, or a pharmaceutically acceptable salt thereof.

18. The compound of claim 4, 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole- 5-carboxylic acid, or a pharmaceutically acceptable salt thereof.

19. The compound of claim 4, 2-propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole -5-carboxylic acid, or a pharmaceutically acceptable salt thereof.

20. The compound of claim 4, 2-propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)-methyl] imidazole-5-carboxylic acid, or a pharmaceutically acceptable salt thereof.

21. The compound of claim 4, 2-propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)-methyl- 5-(hydroxymethyl)imidazole, or a pharmaceutically acceptable salt thereof.

22. The compound of claim 4, 2-butyl-4-trifluoromethyl-1-[(2'-1H-tetrazol-5-yl)biphenyl-4-yl)-methyl]im idazole-5-carboxylic acid, or a pharmaceutically acceptable salt thereof.

23. The compound of claim 4, 2-propyl-4-trifluoromethyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-imidazole-5 -carboxaldehyde, or a pharmaceutically acceptable salt thereof.

24. The compound of claim 4, 2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl] -5-(hydroxymethyl)imidazole, or a pharmaceutically acceptable salt thereof.

25. The compound of claim 4, 2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-4,5-dicar boxylic acid, or a pharmaceutically acceptable salt thereof.

26. The compound of claim 4, 2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl] imidazole-5-carboxylic acid, or a pharmaceutically acceptable salt thereof.

27. The compound of claim 4, 2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl] imidazole-5-carboxaldehyde, or a pharmaceutically acceptable salt thereof.

28. A compound of claim 1 wherein:

R.sup.1 is ##STR521## R.sup.2 is H, Cl, Br, I, F, NO.sub.2, alkyl of 1 to 4 carbon atoms, acyloxy of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, CO.sub.2 H, CO.sub.2 R.sup.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 CF.sub.3, CONHOR.sup.12, SO.sub.2 NH.sub.2, aryl, furyl or ##STR522## R.sup.7 is H, F, Cl, Br, I, NO.sub.2, C.sub.v F.sub.2v+1, where v=1-6, C.sub.6 F.sub.5, or CN,

R.sup.8 is H, CN, alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, or the same groups substituted with F; phenylalkenyl wherein the aliphatic portion is 2 to 6 carbon atoms; --(CH.sub.2).sub.m -imidazol-1-yl; --(CH.sub.2).sub.m -1,2,3-triazolyl optionally substituted with one or two groups selected from CO.sub.2 CH.sub.3 or alkyl of 1 to 4 carbon atoms; --(CH.sub.2).sub.m -tetrazolyl; ##STR523## X is a carbon-carbon single bond, --CO--, --O--, --S--, --NH--, --NR.sup.26 --, --CONR.sup.23 --, NR.sup.23 CO--, --OCH.sub.2 --, --CH.sub.2 O, --SCH.sub.2 --, --CH.sub.2 S--, --NHC(R.sup.27)(R.sup.28)--, --NR.sup.23 SO.sub.2 --, --SO.sub.2 NR.sup.23 --, --C(R.sup.27)(R.sup.28)NH--, --CH.dbd.CH--, --CF.dbd.CF--, --CH.dbd.CF--, --CF.dbd.CH--, ##STR524## or a pharmaceutically suitable salt thereof.

29. A compound of claim 28 wherein R.sup.7 is H, F, Cl, Br, I, NO.sub.2, CF.sub.3, or CN, or a pharmaceutically suitable salt thereof.

30. A compound of claim 29 wherein:

R.sup.1 is ##STR525## R.sup.2 is H, Cl, Br, I, F, NO.sub.2, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, CO.sub.2 H, CO.sub.2 R.sup.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 CF.sub.3, CONHOR.sup.12, SO.sub.2 NH.sub.2, aryl, furyl or ##STR526## R.sup.6 is alkyl of 3 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms or the same groups substituted with one F or one CO.sub.2 R.sup.14 ; cycloalkyl of 3 to 8 carbon atoms; cycloalkylalkyl of 4 to 10 carbon atoms; cycloalkylalkenyl of 5 to 10 carbon atoms; benzyl or benzyl substituted on the phenyl ring with 1 or 2 halogens, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or nitro;

R.sup.8 is alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms, phenylalkenyl wherein the aliphatic portion is 2 to 6 carbon atoms; --(CH.sub.2).sub.m -imidazol-1-yl; --(CH.sub.2).sub.m -1,2,3-triazolyl optionally substituted with one or two groups selected from CO.sub.2 CH.sub.3 or alkyl of 1 to 4 carbon atoms; --(CH.sub.2).sub.m -tetrazolyl; ##STR527## R.sup.10 is alkyl of 1 to 6 carbon atoms or perfluoroalkyl of 1 to 6 carbon atoms, or (CH.sub.2).sub.p C.sub.6 H.sub.5 ;

R.sup.13 is ##STR528## R.sup.16 is H, alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, (CH.sub.2).sub.p C.sub.6 H.sub.5, OR.sup.17, or NR.sup.18 R.sup.19 ;

R.sup.17 is H, alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or phenyl;

R.sup.18 and R.sup.19 independently are H, alkyl of 1 to 4 carbon atoms, phenyl, benzyl, or taken together with the nitrogen form a ring of the formula: ##STR529## X is a carbon-carbon single bond, --CO--, --O--, --S--, --NH--, --NR.sup.26 --, --CONR.sup.23 --, --NR.sup.23 CO--, --OCH.sub.2 --, --CH.sub.2 O, --SCH.sub.2 --, --CH.sub.2 S--, --NHC(R.sup.27)(R.sup.28)--, --NHSO.sub.2 --, --SO.sub.2 NH--, --C(R.sup.27)(R.sup.28)NH--, --CH.dbd.CH--, --CF.dbd.CF--, --CH.dbd.CF--, --CF.dbd.CH--, ##STR530## or a pharmaceutically suitable salt thereof.

31. A compound of claim 2 wherein:

R.sup.2 is H, Cl, Br, I, F, NO.sub.2, alkyl of 1 to 4 carbon atoms, acyloxy of 1to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, CO.sub.2 H, CO.sub.2 R.sup.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 CF.sub.3, CONHOR.sup.12, SO.sub.2 NH.sub.2, aryl, furyl or ##STR531## R.sup.7 is H, F, Cl, Br, I, NO.sub.2, C.sub.v F.sub.2v+1, where v=1-6, C.sub.6 F.sub.5, or CN,

R.sup.13 is --CO.sub.2 H; CO.sub.2 R.sup.9 ; --NHSO.sub.2 CF.sub.3 ; or ##STR532## or a pharmaceutically acceptable salt thereof.

32. A compound of claim 31 wherein R.sup.7 is H, F, Cl, Br, I, NO.sub.2, CF.sub.3, or CN, or a pharmaceutically acceptable salt thereof.

33. A compound of claim 32 wherein:

R.sup.2 is H, Cl, Br, I, F, NO.sub.2, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, CO.sub.2 H, CO.sub.2 R.sup.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 CF.sub.3, CONHOR.sup.12, SO.sub.2 NH.sub.2, aryl, furyl or ##STR533## R.sup.6 is alkyl of 3 to 10 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; benzyl substituted on the phenyl ring with up to 2 groups selected from alkoxy of 1 to 4 carbon atoms, halogen, alkyl of 1 to 4 carbon atoms, and nitro;

R.sup.10 is alkyl of 1 to 6 carbon atoms or perfluoroalkyl of 1 to 6 carbon atoms, or (CH.sub.2).sub.p C.sub.6 H.sub.5 ;

R.sup.16 is alkyl of 1 to 5 carbon atoms, OR.sup.17, or NR.sup.18 R.sup.19 ;

R.sup.17 is H, alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or phenyl;

R.sup.18 and R.sup.19 independently are H, alkyl of 1 to 4 carbon atoms, phenyl, benzyl, or taken together with the nitrogen form a ring of the formula: ##STR534## X is a carbon-carbon single bond, --CO--, --CONR.sup.23 --, --CH.sub.2 CH.sub.2 --, --NR.sup.23 CO--, --OCH.sub.2 --, --O--, --SCH.sub.2 --, --CH.sub.2 S--, --NHCH.sub.2 --, --CH.sub.2 NH-- or --CH.dbd.CH--;

or a pharmaceutically acceptable salt thereof.

34. A compound of claim 3 wherein R.sup.7 is H, Cl, Br, I, CF.sub.3 or C.sub.2 F.sub.5, or a pharmaceutically acceptable salt thereof.

35. A compound of claim 34 wherein R.sup.7 is H, Cl, Br, I, or CF.sub.3, or a pharmaceutically acceptable salt thereof.

36. A compound of claim 35 wherein:

R.sup.2 is H, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms;

R.sup.6 is alkyl of 3 to 7 carbon atoms;

R.sup.7 is H or Cl;

R8 is ##STR535## R.sup.16 is alkyl of 1 to 5 carbon atoms, OR.sup.17, or ##STR536## R.sup.17 is H, alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or phenyl;

or a pharmaceutically acceptable salt thereof.

37. A compound of claim 4 wherein R.sup.7 is H, Cl, Br, I, CF.sub.3 or C.sub.2 F.sub.5, or a pharmaceutically acceptable salt thereof.

38. The compound of claim 4 which is 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-phenyl-2-propylimidazole-5-carboxald ehyde.

39. The compound of claim 4 which is 2-propyl-4-phenyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole- 5-carboxaldehyde.
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