Patent ID: 6294549
Filing Date: 2001-09-25
Classification: A61K

Abstract:
A method for inhibiting a condition selected from the group consisting of restenosis, angiogenesis, diabetic retinopathy, inflammation, and tumor growth in a mammal which comprises administering to the mammal a therapeutically effective amount of a compound of the formula: ##STR167##and pharmaceutically acceptable salts thereof, whereinX isa 5- or 6-membered monocyclic aromatic ring system containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S and either unsubstituted or substituted with R.sup.1 or R.sup.2, ora 9- to 10-membered polycyclic ring system, wherein one or more of the rings is aromatic, containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S and either unsubstituted or substituted with R.sup.1 or R.sup.2,wherein R.sup.1 and R.sup.2 are independently selected from the group consisting ofhydrogen, F, Cl, Br, I,C.sub.1-10 alkyl,C.sub.3-8 cycloalkyl,aryl,aryl C.sub.1-8 alkyl,amino,amino C.sub.1-8 alkyl,C.sub.1-3 acylamino,C.sub.1-3 acylamino C.sub.1-8 alkyl,C.sub.1-6 alkylamino,C.sub.1-6 alkylamino C.sub.1-8 alkyl,C.sub.1-6 dialkylamino,C.sub.1-6 dialkylamino C.sub.1-8 alkyl,C.sub.1-4 alkoxy,C.sub.1-4 alkoxy C.sub.1-6 alkyl,carboxy,carboxy C.sub.1-6 alkyl,C.sub.1-3 alkoxycarbonyl,C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl,carboxy C.sub.1-6 alkyloxy,hydroxy, andhydroxy C.sub.1-6 alkyl;Y is ##STR168##where Z is O, NR.sup.8, or S; and R.sup.8 is defined as R.sup.1 above;R.sup.3 and R.sup.4 are independentlyhydrogen,a five or six membered mono or nine or ten membered polycyclic unsaturated, partially or fully saturated ring system containing 0, 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen or sulfur, either unsubstituted or substituted, with one or more groups selected from hydroxyl, halogen, cyano, trifluoromethyl, C.sub.1-3 alkoxy, C.sub.1-5 alkylcarbonyloxy, C.sub.1-5 alkoxycarbonyl, C.sub.1-5 alkyl, aminoC.sub.1-5 alkyl, hydroxycarbonyl, hydroxycarbonylC.sub.1-5 alkyl, or hydroxycarbonylC.sub.1-5 alkoxy,--(CH.sub.2).sub.n -aryl, wherein n=1-4 and aryl is defined as a five or six membered unsaturated or partially saturated monocyclic ring system, or nine or ten membered polycyclic ring system wherein at least one of the rings is unsaturated or partially saturated and each of the other rings is optionally unsaturated, partially saturated or fully saturated, said aryl group containing 0, 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen and sulfur, either unsubstituted or substituted, with one or more groups selected from hydroxyl, halogen, cyano, trifluoromethyl, C.sub.1-3 alkoxy, C.sub.1-5 alkylcarbonyloxy, C.sub.1-5 alkoxycarbonyl, C.sub.1-5 alkyl, aminoC.sub.1-5 alkyl, hydroxycarbonyl, hydroxycarbonylC.sub.1-5 alkyl, or hydroxycarbonylC.sub.1-5 alkoxy,halogen,hydroxyl,C.sub.1-5 alkylcarbonylamino,arylC.sub.1-5 alkoxy,C.sub.1-5 alkoxycarbonyl,aminocarbonyl,C.sub.1-5 alkylaminocarbonyl,C.sub.1-5 alkylcarbonyloxy,C.sub.3-8 cycloalkyl,oxo,amino,C.sub.1-3 alkylamino,aminoC.sub.1-3 alkyl,arylaminocarbonyl,arylC.sub.1-5 alkylaminocarbonyl,aminocarbonyl,aminocarbonyl-C.sub.1-4 alkyl,hydroxycarbonyl,hydroxycarbonyl C.sub.1-5 alkyl,C.sub.1-6 alkyl, either unsubstituted or substituted, with one or more groups selected from halogen, hydroxyl, C.sub.1-5 alkylcarbonylamino, arylC.sub.1-5 alkoxy, C.sub.1-5 alkoxycarbonyl, aminocarbonyl, C.sub.1-5 alkylaminocarbonyl, C.sub.1-5 alkylcarbonyloxy, C.sub.3-8 cycloalkyl, oxo, amino, C.sub.1-3 alkylamino, aminoC.sub.1-3 alkyl, arylaminocarbonyl, arylC.sub.1-5 alkylaminocarbonyl, aminocarbonyl, aminocarbonyl-C.sub.1-4 alkyl, hydroxycarbonyl, or hydroxycarbonyl C.sub.1-5 alkyl, provided that the carbon atom to which R.sup.3 and R.sup.4 are attached bears only one heteroatom,--(CH.sub.2).sub.m C.ident.CH,--(CH.sub.2).sub.m C.ident.C--C.sub.1-6 alkyl,--(CH.sub.2).sub.m C.ident.C--C.sub.3-7 cycloalkyl,--(CH.sub.2).sub.m C.ident.C-- aryl,--(CH.sub.2).sub.m C.ident.C--C.sub.1-6 alkyl aryl,--(CH.sub.2).sub.m CH.dbd.CH.sub.2,--(CH.sub.2).sub.m CH.dbd.CH C.sub.1-6 alkyl,--(CH.sub.2).sub.m CH.dbd.CH--C.sub.3-7 cycloalkyl,--(CH.sub.2).sub.m CH.dbd.CH aryl,--(CH.sub.2).sub.m CH.dbd.CH C.sub.1-6 alkyl aryl,--(CH.sub.2).sub.m SO.sub.2 C.sub.1-6 alkyl, or--(CH.sub.2).sub.m SO.sub.2 C.sub.1-6 alkylaryl;R.sup.5 ishydrogen,fluorine,C.sub.1-8 alkyl,hydroxyl,hydroxy C.sub.1-6 alkyl,carboxy,carboxy C.sub.1-6 alkyl,C.sub.1-6 alkyloxy;C.sub.3-8 cycloalkyl,aryl C.sub.1-6 alkyloxy,aryl,aryl C.sub.1-6 alkyl,C.sub.1-6 alkylcarbonyloxy,amino,C.sub.1-6 alkylamino,amino C.sub.1-6 alkyl,C.sub.1-6 alkylamino C.sub.1-6 alkyl,aryl amino,aryl amino C.sub.1-6 alkyl,aryl C.sub.1-6 alkylamino,aryl C.sub.1-6 alkylamino C.sub.1-6 alkyl,aryl carbonyloxy,aryl C.sub.1-6 alkylcarbonyloxy,C.sub.1-6 dialkylamino,C.sub.1-6 dialkylamino C.sub.1-6 alkyl,C.sub.1-6 alkylaminocarbonyloxy,C.sub.1-8 alkylsulfonylamino,C.sub.1-8 alkylsulfonylamino C.sub.1-6 alkyl,aryl sulfonylamino C.sub.1-6 alkyl,aryl sulfonylamino,aryl C.sub.1-6 alkylsulfonylamino,aryl C.sub.1-6 alkylsulfonylamino C.sub.1-6 alkyl,C.sub.1-8 alkyloxycarbonylamino,C.sub.1-8 alkyloxycarbonylamino C.sub.1-8 alkyl,aryl C.sub.1-8 alkyloxycarbonylamino,aryl oxycarbonylamino,aryl oxycarbonylamino C.sub.1-8 alkyl,aryl C.sub.1-8 alkyloxycarbonylamino C.sub.1-8 alkyl,C.sub.1-8 alkylcarbonylamino,C.sub.1-8 alkylcarbonylamino C.sub.1-6 alkyl,aryl carbonylamino C.sub.1-6 alkyl,aryl carbonylamino,aryl C.sub.1-6 alkylcarbonylamino,aryl C.sub.1-6 alkylcarbonylamino C.sub.1-6 alkyl,C.sub.1-8 alkylaminocarbonylamino,aminocarbonylamino,aminocarbonylamino C.sub.1-6 alkyl,C.sub.1-8 alkylaminocarbonylamino C.sub.1-6 alkyl,aryl aminocarbonylamino C.sub.1-6 alkyl,aryl aminocarbonylamino,aryl C.sub.1-8 alkylaminocarbonylamino,aryl C.sub.1-8 alkylaminocarbonylamino C.sub.1-6 alkyl,aminosulfonylamino C.sub.1-6 alkyl,aminosulfonylamino,C.sub.1-8 alkylaminosulfonylamino,C.sub.1-8 alkylaminosulfonylamino C.sub.1-6 alkyl,aryl aminosulfonylamino C.sub.1-6 alkyl,aryl aminosulfonylamino,aryl C.sub.1-8 alkylaminosulfonylamino,aryl C.sub.1-8 alkylaminosulfonylamino C.sub.1-6 alkyl,C.sub.1-6 alkylsulfonyl,C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,aryl sulfonyl,aryl sulfonyl C.sub.1-6 alkyl,aryl alkylsulfonyl,aryl C.sub.1-6 alkylsulfonyl,aryl C.sub.1-6 alkylsulfonyl C.sub.1-6 alkyl,C.sub.1-6 alkylcarbonyl,C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,aryl carbonyl C.sub.1-6 alkyl,aryl carbonyl,aryl C.sub.1-6 alkylcarbonyl,aryl C.sub.1-6 alkylcarbonyl C.sub.1-6 alkyl,C.sub.1-6 alkylthiocarbonylamino,C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,aryl thiocarbonylanmino C.sub.1-6 alkyl,aryl thiocarbonylamino,aryl C.sub.1-6 alkylthiocarbonylamino,aryl C.sub.1-6 alkylthiocarbonylamino C.sub.1-6 alkyl,aminocarbonyl C.sub.1-6 alkyl,aminocarbonyl,C.sub.1-8 alkylaminocarbonyl,C.sub.1-8 alkylaminocarbonyl C.sub.1-6 alkyl,aryl aminocarbonyl C.sub.1-6 alkyl,aryl aminocarbonyl,aryl C.sub.1-8 alkylaminocarbonyl,aryl C.sub.1-8 alkylaminocarbonyl C.sub.1-6 alkyl,wherein alkyl groups and aryl groups are optionally unsubstituted or substituted with one or more substituents selected from R.sup.1 and R.sup.2 ; andR.sup.6, R.sup.7, and R.sup.9 are independentlyhydrogen,C.sub.1-8 alkyl,aryl,aryl C.sub.1-8 alkyl,hydroxy,C.sub.1-8 alkyloxy,aryloxy,aryl C.sub.1-6 alkyloxy,C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyloxy,aryl C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyloxy,C.sub.1-8 alkylaminocarbonylmethyleneoxy, orC.sub.1-8 dialkylaminocarbonylmethyleneoxy,and wherein m and n are integers 0-6.