Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-11-15
1995-09-05
Higel, Floyd D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514341, 546278, 548251, 548252, 548253, 5483151, 5483154, A61K 31415, A61K 3144, C07D40114, C07D40914, C07D40514
Patent
active
054479495
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US92/04071 filed May 14, 1992.
The present invention relates to new N-(heteroaryl)-imidazolyl-alkenoic acids which are angiotensin II receptor antagonists and are useful in regulating hypertension induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure, and glaucoma. This invention also relates to pharmaceutical compositions containing these compounds and methods for using these compounds as antagonists of angiotensin II, as antihypertensive agents and as agents for treating congestive heart failure, renal failure, and glaucoma.
BACKGROUND OF THE INVENTION
The class of peptide pressor hormone known as angiotensin is responsible for a vasopressor action that is implicated in the etiology of hypertension in man. Inappropriate activity of the renin-angiotensin systems appears to be a key element in essential hypertension, congestive heart failure and in some forms of renal disease. In addition to a direct action on arteries and arterioles, angiotensin II (AII), being one of the most potent endogenous vasoconstrictors known, exerts stimulation on the release of aldosterone from the adrenal cortex. Therefore, the renin-angiotensin system, by virtue of its participation in the control of renal sodium handling, plays an important role in cardiovascular hemeostasis.
Interruption of the renin-angiotensin system with converting enzyme inhibitors, such as captopril, has proved to be clinically useful in the treatment of hypertension and congestive heart failure (Abrams, W. B., et al., (1984), Federation Proc., 43, 1314). The most direct approach towards inhibition of the renin-angiotensin system would block the action of AII at the receptor. Compelling evidence suggests that AII also contributes to renal vasoconstriction and sodium retention that is characteristic of a number of disorders such as heart failure, cirrhosis and complications of pregnancy (Hollenberg, N. K., (1984), J. Cardiovas. Pharmacol., 6, S176). In addition, recent animal studies suggest that inhibition of the renin-angiotensin system may be beneficial in halting or slowing the progression of chronic renal failure (Anderson, S., et al., (1985), J. Clin. Invest., 76, 612). Also, a recent patent application (South African Patent Application No. 87/01,653) claims that AII antagonists are useful as agents for reducing and controlling elevated intraocular pressure, especially glaucoma, in mammals.
The compounds of this invention inhibit, block and antagonize the action of the hormone AII, and are therefore useful in regulating and moderating angiotensin induced hypertension, congestive heart failure, renal failure and other disorders attributed to the actions of AII. When compounds of this invention are administered to mammals, the elevated blood pressure due to AII is reduced and other manifestations based on AII intercession are minimized and controlled. Compounds of this invention are also expected to exhibit diuretic activity.
Recognition of the importance of blocking and inhibiting the actions of AII has stimulated other efforts to Synthesize antagonists of AII. The following references have disclosed imidazole derivatives which are described as having AII blocking activity and useful as hypotensive agents.
Furukawa et al., U.S. Pat. No. 4,340,598 discloses imidazol-5-yl-acetic acids and imidazol-5-yl-propanoic acids. Specifically, the discloser includes 1-benzyl-2-n-butyl-5-chloroimidazole-4-acetic acid and 1-benzyl-2-phenyl-5-chloroimidazole-4-propanoic acid.
Furukawa, et al., U.S. Pat. No. 4,355,040 discloses substituted imidazole-5-acetic acid derivatives. A compound specifically disclosed is 1-(2-chlorobenzyl)-2-n-butyl-4-chloroimidazole-5-acetic acid.
Carini et al. in EP 253,310 disclose certain imidazolylpropenoic acids. Two intermediates described in this patent are ethyl 3-[1-(4-nitrobenzyl)-2-butyl-4-chloroimidazol-5-yl]propenoate and ethyl 3-[2-butyl-4-chloro-1-(4-aminobenzyl)imidazol-5-yl]propenoate.
Also, Wareing, in PCT/EP 86/00297, discloses as inte
REFERENCES:
patent: 4006137 (1977-02-01), Haugwitz et al.
patent: 4987146 (1991-01-01), Rohde et al.
patent: 5177096 (1993-01-01), Keenan et al.
patent: 5185351 (1993-02-01), Finkelstein et al.
patent: 5198438 (1993-03-01), Allen et al.
patent: 5234917 (1993-08-01), Finkelstein et al.
patent: 5248689 (1993-09-01), Girard et al.
patent: 5312828 (1994-05-01), Finkelstein et al.
Weinstock et al, J. Med. Chem., vol. 34, pp. 1514-1517 (1991).
Girard Gerald R.
Hill David T.
Weinstock Joseph
Higel Floyd D.
Lentz Edward T.
McCarthy Mary E.
SmithKline Beecham Corporation
Venetianer Stephen
LandOfFree
N-(heteroaryl) imidazolyl-alkenoic acids having angiotension II does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with N-(heteroaryl) imidazolyl-alkenoic acids having angiotension II , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-(heteroaryl) imidazolyl-alkenoic acids having angiotension II will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-473016