Inhibitors of platelet-derived growth factor
AssigneeSchering Corporation
InventorsJohn W. Clader, Harry R. Davis, Deborra Mullins, Stuart Rosenblum, Jay Weinstein
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Abstract
A method of inhibiting the binding of PDGF using compounds of the formula I ##STR1## useful in the treatment of atherosclerosis, cancer, retinal detachment, pulmonary fibrosis, arthritis, psoriasis and glomerulonephritis, and restenosis following angioplasty or vascular surgery is disclosed. Also disclosed are pharmaceutical compositions and novel PDGF inhibitory compounds of the formula ##STR2## or a pharmaceutically acceptable addition salt thereof, useful in the treatment of atherosclerosis, cancer, retinal detachment, pulmonary fibrosis, arthritis, psoriasis and glomerulonephritis, and restenosis following angioplasty or vascular surgery.
Claims12
A compound of the formula ##STR37## or a pharmaceutically acceptable addition salt thereof, wherein R.sup.a is an aryl group substituted by 1-5 substitutents R.sup.4a ;
- R.sup.1a and R.sup.2a together comprise a fused ring of the formula ##STR38## q is 0 or 1 R.sup.3a is nitro;
- and
- wherein the R.sup.4a substituents are independently selected from the group consisting of hydroxy, Y-substituted alkyl, alkylamino, dialkylamino, aryl amino, diarylamino, trialkylammonium, thio, --S(O).sub.m R.sup.7, --SO.sub.3, carboxyl, alkoxycarbonyl, benzyloxycarbonyl, alkenyloxycarbonyl, carboxamido, N-phthalimido, cyanoalkoxycarbonyl, carboxyalkoxycarbonyl, benzyloxycarbonyl-alkoxycarbonyl, N,N-dialkylcarboxamido, trifluoromethyl and cyano;
- Y is selected from the group consisting of halogeno, trialkylammonium, amino, carboxy, pyridinium, triarylphosphonium, benzyloxycarbonyl, hexamethylenetetraminium, --N.dbd.CH--alkyl, --N.dbd.CH--aryl and --N.dbd.CH--N(alkyl).sub.2 ;
- R.sup.7 is C.sub.1 -C.sub.8 alkyl or aryl;
- and
- m is 0, 1 or 2.
A method of inhibiting the binding of platelet-derived growth factor by treating a mammal in need of such treatment with a inhibitory effective dose of a compound of the formula ##STR104## or a pharmaceutically acceptable addition salt thereof, wherein p is 0, 1, 2, 3, 4, 5, or 6 and R is hydrogen or an aryl group substituted by 1-5 substitutents R.sup.4, provided that R is not hydrogen when p=0;
- R.sup.1 and R.sup.2 taken together comprise a fused ring of the formula ##STR105## q is 0, 1, 2, 3 or 4;
- X and R.sup.3 are independently selected from the group consisting of hydrogen, halogeno, hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 alkenyl, C.sub.1 -C.sub.8 alkoxy, aryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, trialkylammonium, thio, --S(O).sub.2 R.sup.6, --S(O).sub.m R.sup.7, --SO.sub.3, nitro, --NHS(O).sub.2 alkyl, carboxyl, alkoxycarbonyl, carboxamido, N-alkylcarboxamido, N,N-dialkylcarboxamido, alkylcarbonylamino, arylcarbonylamino, alkylaminocarbonyloxy, alkoxycarbonyloxyl, alkylcarbonyloxy, trifluoromethyl, cyano, aryl, and substituted aryl, wherein the substitutents are 1-5 groups R.sup.4 ;
- and wherein the R.sup.4 substituents are independently selected from the group consisting of hydrogen, halogeno, C.sub.1 -C.sub.8 alkenyl, C.sub.1 -C.sub.8 alkynyl, hydroxy, C.sub.1 -C.sub.8 alkyl, Y-substituted alkyl, C.sub.1 -C.sub.8 alkoxy, aryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, trialkylammonium, thio, --SO.sub.2 R.sup.6, --S(O).sub.m R.sup.7, --SO.sub.3, nitro, carboxy, alkoxycarbonyl, benzyloxycarbonyl, alkenyloxycarbonyl, carboxamido, N-phthalimido, cyanoalkoxycarbonyl, carboxyalkoxycarbonyl, benzyloxycarbonylalkoxycarbonyl, N-alkylcarboxamido, N,N-dialkylcarboxamido, trifluoromethyl, cyano and aryl;
- Y is selected from the group consisting of halogeno, trialkylammonium, amino, carboxy, pyridinium, triarylphosphonium, benzyloxycarbonyl, hexamethylenetetraminium, --N.dbd.CH--alkyl, --N.dbd.CH--aryl and --N.dbd.CH--N(alkyl).sub.2 ;
- R.sup.6 is amino, arylamino, alkylamino or dialkylamino;
- R.sup.7 is C.sub.1 -C.sub.8 alkyl or aryl;
- and
- m is 0, 1 or 2.
Dependencies are inferred from the claim text.