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US 5,310,929 AGranted
Prodrugs of imidazole carboxylic acids as angiotensin II receptor antagonists
AssigneeE. I. Du Pont de Nemours and Company
InventorsRobert J. Ardecky, Carol L. Ensinger, James R. Pruitt
Life of this patent
Estimating the term…
Abstract
Prodrugs of imidazole carboxylic acids which are AII antagonists useful in treating hypertension, pharmaceutical compositions thereof and a method of treating hypertension using such prodrugs are disclosed.
Claims10
A compound of the formula:
- ##STR26## wherein R.sup.1 is --CO.sub.2 H or ##STR27## R.sup.2 is (a) H,
- (b) C1-C5-alkyl,
- (c) C1-C5-alkoxy,
- (d) halo (F, Cl),
- (e) phenyl;
- R.sup.3 is C1-C5-alkyl, C2-C5-alkenyl, C2-C5-alkynyl;
- R.sup.4 is
- (a) H,
- (b) halo (Cl, Br, I),
- (c) C1-C6-alkyl,
- (d) C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
- R.sup.5 is
- (a) --(CH.sub.2).sub.p NR.sup.12 R.sup.13,
- (b) --(CH.sub.2).sub.s CH(R.sup.7)(CH.sub.2).sub.s, O.sub.2 CR.sup.8,
- (c) ##STR28## (d) --(CH.sub.2).sub.p CO.sub.2 R.sup.10, (e) ##STR29## R.sup.6 is (a) H,
- (b) halogen (F, Cl, Br, I),
- (c) C1-C5-alkyl,
- (d) --OH,
- (e) C1-C4-alkoxy,
- (f) --NO.sub.2,
- (g) --NR.sup.12 R.sup.13,
- (h) --NR.sup.12 COR.sup.15,
- (i) --NR.sup.12 CO.sub.2 R.sup.15,
- (j) --S(O).sub.r R.sup.14 where r is 0, 1 or 2,
- (h) --CO.sub.2 R.sup.15,
- (i) --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1),
- (J) --OC.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1), or (K) --CN;
- R.sup.7 is H or C1-C4-alkyl;
- R.sup.8 is
- (a) H,
- (b) C1-C5-alkyl,
- (c) C1-C5-alkyl optionally substituted with a group consisting of:
- i) C1-C5-alkoxy,
- ii) aryl, wherein aryl is phenyl or napthyl optionally substituted with one or two substituents selected from the group consisting of halo (F, Cl, Br, I), C1-C4-alkyl, C1-C4-alkoxy, --NO.sub.2, --S(O).sub.r (C1-C5-alkyl), --OH, --NR.sup.12 R.sup.13, --CO.sub.2 R.sup.15, and --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
- R.sup.9 is
- (a) C1-C5-alkyl,
- (b) --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1),
- (c) C1-C5-alkyl optionally substituted with a group consisting of:
- i) C1-C5-alkoxy,
- ii) phenyl or phenyl substituted with at least one substituent selected from the group consisting of halo (F, Cl, Br, I), C1-C4-alkyl, C1-C4-alkoxy, --NO.sub.2, --S(O).sub.r (C1-C4-alkyl), --OH,--NR.sup.12 R.sup.13, --CO.sub.2 R.sup.15, and --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1),
- iii) benzyl or benzyl substituted with at least one substituent selected from the group consisting of halo (F, Cl, Br, I), C1-C4-alkyl C1-C4-alkoxy, --NO.sub.2, --S(O).sub.r (C1-C4-alkyl), --OH,--NR.sup.12 R.sup.13, --CO.sub.2 R.sup.15, and --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
- R.sup.10 is
- (a) phenyl or phenyl substituted with at least one substituent selected from the group consisting of halo (F, Cl, Br, I), C1-C4-alkyl C1-C4-alkoxy, --NO.sub.2, --S(O).sub.r (C1-C4-alkyl), --OH,--NR.sup.12 R.sup.13, --CO.sub.2 R.sup.15, and --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
- (b) benzyl or benzyl substituted with at least one substituent selected from the group consisting of halo (F, Cl, Br, I), C1-C4-alkyl C1-C4-alkoxy, --NO.sub.2, --S(O).sub.r (C1-C4-alkyl), --OH,--NR.sup.12 R.sup.13, --CO.sub.2 R.sup.15, and --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
- R.sup.11 is H, C1-C5-alkyl or benzyl;
- R.sup.12 and R.sup.13 are independently H, C1-C5-alkyl, phenyl or benzyl;
- R.sup.14 is CF.sub.3, C1-C5-alkyl, or phenyl;
- R.sup.15 is H, C1-C5-alkyl, or NR.sup.12 R.sup.13 ;
- R.sup.16 is H or CH.sub.2 O.sub.2 CC(CH.sub.3).sub.3 ;
- p is 1-5;
- r is 0-2;
- s and s' are 0-5;
- t is 0 or 1;
- or a pharmaceutically acceptable salt thereof.
51 more elements
Dependencies are inferred from the claim text.