Patent ID: 6265410
Filing Date: 2001-07-24
Classification: A61K,A61P,C07D

Abstract:
A compound of Formula II ##STR50##where:any two contiguous positions in positions A, B, D and E taken together is a single heteroatom selected from the group consisting of nitrogen, oxygen or sulfur, and the other two remaining atoms are carbon;X=O, S, NH or NR.sup.7, such that R.sup.7 =lower alkyl (1-4 carbon atoms), OH, NH.sub.2, lower alkoxy (1-4 carbon atoms) or lower monoalkylamino (1-4 carbon atoms);n=0, 1, 2;R.sup.1 =H or lower alkyl (1-4 carbon atoms); if n=2, R.sup.1 can be independently H or lower alkyl (1-4 carbon atoms) on either linking carbon atom;R.sup.2 is lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), lower alkoxy (1-4 carbon atoms), cycloalkoxy (3-8 carbon atoms), nitro, halo (fluoro, chloro, bromo, iodo), lower perfluoroalkyl (1-4 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms; --O--C(O)R), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms), hydroxymethyl, lower acyl (1-4 carbon atoms; --C(O)R), cyano, lower thioalkyl (1-4 carbon atoms), lower sulfinylalkyl (1-4 carbon atoms), lower sulfonylalkyl (1-4 carbon atoms), thiocycloalkyl (3-8 carbon atoms), sulfinylcycloalkyl (3-8 carbon atoms), sulfonylcycloalkyl (3-8 carbon atoms), sulfonamido, lower mono or dialkylsulfonamido (1-4 carbon atoms), mono or dicycloalkylsulfonamido (3-8 carbon atoms), mercapto, carboxy, carboxamido (--C(O)--NH.sub.2), lower mono or dialkylcarboxamido (1-4 carbon atoms), mono or dicycloalkylcarboxamido (3-8 carbon atoms), lower alkoxycarbonyl (1-4 carbon atoms), cycloalkoxycarbonyl (3-8 carbon atoms), lower alkenyl (2-4 carbon atoms), cycloalkenyl (4-8 carbon atoms), lower alkynyl (2-4 carbon atoms), or two R.sup.2 taken together on contiguous carbon atoms can form a carbocyclic ring of 5-7 members or a monounsaturated 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, firanyl, pyrrolidyl, piperidinyl, thiolanyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morpholino or thiomorpholino ring; andm=0-3,Ar is an aromatic rind selected from the group consisting of phenyl, thienyl, furanyl, pyrrolyl, pyridyl, pyrimidyl, imidazoyl, pyrazinyl, oxazolyl, thiazolyl, naphthyl, benzothienyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl and quinazolinyl;R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from the group consisting of H, lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), lower alkoxy (1-4 carbon atoms), cycloalkoxy (3-8 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms); carbonato (--OC(O)OR) where the R is lower alkyl of 1 to 4 carbon atoms or cycloalkyl of 3-8 carbon atoms;ureido or thioureido or N- or O-linked urethane any one of which is optionally substituted by mono or di-lower alkyl (1-4 carbon atoms) or cycloalkyl (3-8 carbon atoms);lower thioalkyl (1-4 carbon atoms), thiocycloalkyl (3-8 carbon atoms), mercapto, lower alkenyl (2-4 carbon atoms), hydrazino, N'-lower alkylhydrazino (1-4 carbon atoms), lower acylamino (1-4 carbon atoms), hydroxylamino, and lower O-alkylhydroxylamino (1-4 carbon atoms);or optionally R.sup.3 and R.sup.4 or R.sup.4 and R.sup.6 taken together on contiguous carbon atoms forms a monounsaturated 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, furanyl, pyrrolidyl, piperidinyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morpholino or thiomorpholino ring;any lower alkyl group substituent on any of the substituents in R.sup.3 -R.sup.6 which contain such a moiety can be optionally substituted with one or more of hydroxy, amino, lower monoalkylamino, lower dialkylamino, N-pyrrolidyl, N-piperidinyl, N-pyridinium, N-morpholino, N-thiomorpholino or N-piperazino groups;R.sup.8 is hydrogen, lower alkyl (1-4 carbon atoms), amino or mono or dialkyl (1-4 carbon atoms) amino;with the proviso that R.sup.3 cannot be either OH or SH;with the further proviso that at least one of the R.sup.3 and R.sup.4 or R.sup.4 and R.sup.6 substituents must be other than hydrogen, halogen, lower alkyl (1-4 carbon atoms) or lower alkoxy (1-4 carbon atoms);optionally if any of the substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4 or R.sup.6 have chiral centers, then all stereoisomers thereof both as racemic and/or diastereoisomeric mixtures are included;or a pharmaceutical salt or hydrate thereof.