Patent ID: 6319939
Filing Date: 2001-11-20
Classification: A61P,C07D

Abstract:
A compound having the formula ##STR44##a N-oxide, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein:X represents --O--, --S-- or --NR.sup.3 --;R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl or aryl;R.sup.2 represents hydrogen; C.sub.1-12 alkyl; C.sub.3-7 cycloalkyl; C.sub.2-8 alkenyl; aryl; Het.sup.1 ; or C.sub.1-12 alkyl substituted with one or two substituents selected from C.sub.3-7 cycloalkyl, hydroxy, C.sub.1-4 alkyloxy, cyano, amino, mono- and di(C.sub.1-4 alkyl)amino, mono- or di(arylC.sub.1-4 alkyl)amino, di(arylC.sub.1-4 alkyl)aminocarbonyloxy, (C.sub.1-4 alkyl) (arylC.sub.1-4 alkyl)amino, mono- and di(aryl)amino, (C.sub.1-4 alkyl) (di(C.sub.1-4 alkyl)aminoC.sub.1-4 alkyl)amino, pyrrolidinyl, piperidinyl, piperazinyl optionally substituted with C.sub.1-4 alkyl, morpholinyl, perhydro-azepinyl, carboxyl, C.sub.1-4 alkyloxycarbonyl, aminocarbonyl, mono- and di(C.sub.1-4 alkyl)aminocarbonyl, aryl, aryloxy and arylthio;R.sup.3 represents hydrogen, C.sub.1-6 alkyl, aryl, Het.sup.1 or C.sub.1-6 alkyl substituted with aryl or Het.sup.1 ;R.sup.4 represents C.sub.1-12 alkyl substituted with one, two or three substituents each independently selected from hydroxy, mercapto, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, aryloxy, arylthio, Het.sup.1 -oxy, Het.sup.1 -thio, C.sub.3-7 cycloalkyl optionally substituted with hydroxycarbonylC.sub.1-6 alkyl, carboxyl, C.sub.1-6 alkyloxycarbonyl, arylC.sub.1-6 alkyloxy, arylC.sub.1-6 alkylthio, aryl, Het.sup.1 ; C.sub.2-8 alkenyl optionally substituted with one, two or three substituents selected from halo, C.sub.3-7 cycloalkyl, Het.sup.1 ; C.sub.2-8 alkynyl optionally substituted with halo, C.sub.3-7 cycloalkyl, aryl; C.sub.3-7 cycloalkyl optionally substituted with C.sub.1-6 alkyl or aryl; C.sub.5-7 cycloalkenyl optionally substituted with C.sub.1-6 alkyl or aryl; aryl; Het.sup.1 ; or--Alk--NR.sup.3 R.sup.5 (i)wherein Alk represents C.sub.1-6 alkanediyl; andR.sup.5 represents hydrogen, C.sub.1-6 alkyl, aryl, Het.sup.1, (aryl or Het.sup.1)C.sub.1-6 alkyl, (aryl or Het.sup.1)carbonyl or (aryl or Het.sup.1)C.sub.1-6 alkyloxycarbonyl;aryl represents indanyl, indenyl, naphtyl, 5,6,7,8-tetrahydro-2-naphtalenyl, phenyl; said indanyl, indenyl, naphtyl or phenyl may be substituted with one, two, three, four or five substituents each independently selected from hydroxy, halo, nitro, cyallo, amino, azido, mono- or di(C.sub.1-6 alkyl)-amino, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 alkyl, polyhaloC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, phenyl, phenyloxy, phenylC.sub.1-6 alkyloxy, pyridinylC.sub.1-6 alkyloxy, C.sub.1-6 alkyloxy, formyl, carboxyl and C.sub.1-6 alkylcarbonyl; or two adjacent carbon atoms on said phenyl may be substituted by a single bivalent radical having the formula C.sub.1-12 alkanediyl or polyhaloC.sub.1-12 alkanediyl;Het represents an unsaturated heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, or tetrazolyl; each of said unsaturated heterocycles may optionally be substituted with amino, mercapto, C.sub.1-6 alkyl, C.sub.1-6 alkylthio or aryl; andHet.sup.1 represents a monocyclic heterocycle selected from pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,3,4-triazolyl, 1,2,4-triazolyl, tetrahydrofuranyl, furanyl, thiolanyl, thienyl, dioxolanyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, isoxazolidinyl, oxazolidinyl, isothiazolidinyl, thiazolidinyl, piperidinyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, tetrahydropyranyl, pyranyl, morpholinyl and dioxanyl; each of said monocyclic heterocycles may be optionally substituted with one or two substituents each independently selected from C.sub.1-4 alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C.sub.1-4 alkyloxycarbonyl; or a bicyclic heterocycle selected from indolinyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzofuranyl, benzothienyl, 2H-1-benzopyranyl, 3,4-dihydro-2H-1-benzopyranyl, benzthiazolyl, isoquinolinyl, quinolinyl, 3,4-dihydroquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, chromanyl, 1,4-benzodioxinyl, 1,4-benzoxathianyl, benzodioxanyl and benzodioxolanyl; each of said bicyclic heterocycles may be substituted with one or two substituents each independently selected from C.sub.1-4 alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C.sub.1-4 alkyloxycarbonyl.