Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-06-10
1995-02-07
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3138
Patent
active
053876016
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Interruption of the renin-angiotensin system (RAS) with converting enzyme inhibitors, such as captopril, has proved clinically useful in the treatment of certain disease states, such as hypertension and congestive heart failure [Abrams, et al., Federation Proc., 43:1314 (1984)]. Furthermore, evidence suggests that inhibition of this system may be beneficial in the prevention of restinosis after angioplasty or bypass surgery. Since AII is the biologically active component of the reninangiotensin system responsible for the system's peripheral effects, the most direct approach towards inhibition of RAS and in particular the prevention of restinosis after angioplasty or bypass surgery would be blockade of angiotensin II at its receptor.
SUMMARY OF THE INVENTION
The present invention provides a new method of the prevention of restinosis after angioplasty or bypass surgery in a mammal which comprises administering to a subject in need thereof an effective non-toxic amount of an angiotensin II receptor antagonist.
The present invention also provides for the use of an angiotensin II receptor antagonist in the manufacture of a medicament for the prevention of restinosis after angioplasty or bypass surgery.
DESCRIPTION OF THE INVENTION
The present invention is a therapeutic method for the prevention of restinosis after angioplasty or bypass surgery in mammals. The method utilizes a class of antagonists which have been previously prepared and evaluated as effective AII receptor antagonists. Examples of suitable angiotensin II receptor antagonists include, but are not limited to, the following:
Substituted imidazoles of the formula (I), which are described in U.S. application Ser. No. 07/746,262, filed Aug. 14, 1991: ##STR1## in which: R.sup.1 is adamantyl, phenyl, biphenyl, or naphthyl, with each aryl group being unsubstituted or substituted by one to three substituents selected from Cl, Br, F, I, C.sub.1 -C.sub.6 alkyl, nitro, A--CO.sub.2 R.sup.7, tetrazol-5-yl, C.sub.1 -C.sub.6 alkoxy, hydroxy, SC.sub.1 --C.sub.6 alkyl, SO.sub.2 NHR.sup.7, NHSO.sub.2 R.sup.7, SO.sub.3 H, CONR.sup.7 R.sub.7, CN, SO.sub.2 C.sub.1 -C.sub.6 alkyl, NHSO.sub.2 R.sup.7, PO(OR.sup.7).sub.2, NR.sup.7, NR.sup.7 COH, NR.sup.7 COC.sub.1 -C.sub.6 alkyl, NR.sup.7 CON(R.sup.7).sub.2, NR.sup.7 COW, W, SO.sub.2 W; -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, or (CH.sub.2).sub.0-8 phenyl unsubstituted or substituted by one to three substituents selected from C.sub.1 -C.sub.6 alkyl, nitro, Cl, Br, F, I, hydroxy, C.sub.1 -C.sub.6 alkoxy, NR.sup.7 R.sup.7, CO.sub.2 R.sup.7, CN, CONR.sup.7 R.sup.7, W, tetrazol-5-yl, NR.sup.7 COC.sub.1 -C.sub.6 alkyl, NR.sup.7 COW, SC.sub.1 -C.sub.6 alkyl, SO.sub.2 W, or SO.sub.2 C.sub.1 -C.sub.6 alkyl; CONR.sup.7 R.sup.7, NO.sub.2, W, CN, NR.sup.7 R.sup.7, or phenyl; thienyl-Y-, furyl-Y-, pyrazolyl-Y-, imidazolyl-Y-, pyrrolyl-Y-, triazolyl-Y-, oxazolyl-Y-, isoxazolyl-Y-, thiazolyl-Y-, pyridyl-Y-, or tetrazolyl-Y-, except that R.sup.4 and R.sup.5 are not both selected from hydrogen and C.sub.1 -C.sub.6 alkyl and each heterocyclic ring is unsubstituted or substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, Cl, Br, F, I, NR.sup.7 R.sup.7, CO.sub.2 R.sup.7, SO.sub.2 NHR.sup.7, SO.sub.3 H, or CONR.sup.7 R.sup.7, OH, NO.sub.2, W, SO.sub.2 W, SC.sub.1 -C.sub.6 alkyl, SO.sub.2 C.sub.1 -C.sub.6 alkyl, NR.sup.7 COH, NR.sup.7 COW, or NR.sup.7 COC.sub.1 -C.sub.6 alkyl; branched or optionally substituted by phenyl or benzyl, wherein each of the aryl groups is unsubstituted or substituted by halo, NO.sub.2, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, CN, or CO.sub.2 R.sup.7 ; optionally substituted by C.sub.1 -C.sub.6 alkyl, one or two benzyl groups, thienylmethyl, or furylmethyl, or --C(O)NHCHR.sup.9 --, wherein R.sup.9 is H, C.sub.1 -C.sub.6 alkyl, phenyl, benzyl, thienylmethyl, or furylmethyl; --S(CH.sub.2).sub.n --; (CH.sub.2).sub.m phenyl, wherein m is 0-4; and alkyl)amino-2-oxoethyl; or a pharmaceutically acceptable salt thereof.
Preferred compounds included withi
REFERENCES:
patent: 5185351 (1993-02-01), Finkelstein et al.
patent: 5250519 (1993-10-01), Conrad et al.
Lentz Edward T.
McCarthy Mary E.
Peabody John
Richter Johann
SmithKline Beecham p.l.c.
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