Patent ID: 6143747
Filing Date: 2000-11-07
Classification: A61P,C07C,C07D

Abstract:
A compound represented by the formula: ##STR340## or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.1 represents hydrogen, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 CH.sub.3, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --C(CH.sub.3).sub.2 (SH), --C(CH.sub.3).sub.2 (SCH.sub.3), --C(CH.sub.3).sub.2 (S[O]CH.sub.3), --C(CH.sub.3).sub.2 (S[O].sub.2 CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl, aminosulfonylalkyl, N-alkylaminosulfonylalkyl, N,N-dialkylaminosulfonylalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl radicals, an amino acid side chain of asparagine, lysine, aspartic acid, aspartic acid methyl ester, methionine or the sulfoxide (SO) or sulfone (SO.sub.2) derivatives thereof, S-methyl cysteine or the sulfoxide (SO) or sulfone (SO.sub.2) derivatives thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, histidine, norleucine, glutamine, threonine, allo-threonine, serine, O-alkyl serine, beta-cyano alanine or valine;R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl, aralkyl, heteroaryl or heteroaralkyl radicals, which radicals are optionally substituted with one or more alkyl, halogen, --NO.sub.2, --CN, --CF.sub.3, --OR.sup.9 or --SR.sup.9 radicals, wherein R.sup.9 represents hydrogen, alkyl, aryl, heteroaryl, cycloalkyl or heterocyclo radicals;R.sup.3 represents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heteroaryl, heterocycloalkyl, aryl, aralkyl, heteroaralkyl, thioalkyl, alkylthioalkyl or arylthioalkyl radicals or the corresponding sulfone or sulfoxide derivatives thereof, aminoalkyl or N-mono- or N,N-disubstituted aminoalkyl radicals, wherein said substituents are alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclo, or heterocycloalkyl radicals;R.sup.4 represents alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, optionally substituted or heterocyclo heteroaryl, heterocycloalkyl, optionally substituted aryl, aralkyl, aralkenyl, heteroaralkyl, alkoxycarbonylaminoheteroaryl, thioalkyl, alkylthioalkyl or arylthioalkyl radicals or the corresponding sulfone or sulfoxide derivatives thereof, aminoalkyl or N-mono- or N,N-disubstituted aminoalkyl radicals, wherein said substituents are alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclo, or heterocycloalkyl radicals, thioalkyl, alkylthioalkyl or arylthioalkyl radicals or the corresponding sulfone or sulfoxide derivatives thereof;R.sup.6 represents hydrogen or alkyl radicals;each R.sup.7 independently represents carboxy, amidino or N-alkylamidino radicals, or radicals as defined for R.sup.1 ; or R.sup.7 together with R.sup.1 and the carbon atoms to which R.sup.1 and R.sup.7 are attached, represent cycloalkyl or heterocyclo radicals;each R.sup.8 independently represents hydrogen or alkyl radicals;R.sup.10 and R.sup.11 each independently represent hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heteroarylcarbonylalkyl, arylcarbonylalkyl, thioalkyl, alkylthioalkyl or arylthioalkyl radicals or the corresponding sulfone or sulfoxide derivatives thereof, aminoalkyl or N-mono- or N,N-disubstituted aminoalkyl radicals, wherein said substituents are alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclo or heterocycloalkyl radicals; or R.sup.10 and R.sup.11 together with the nitrogen to which they are attached represent aralkylheteroaryl, aralkylheterocyclo, heteroaralkylheteroaryl or heteroaralkylheterocyclo radicals;x and w each represent 0, 1 or 2;t represents 0-6;Y represents O, S or NH andwherein alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having from 1 to 10 carbon atoms, alkenyl, alone or in combination, means a straight-chain or branched-chain hydrocarbon radical having one or more double bonds and from 2 to 10 carbon atoms; alkynyl, alone or in combination, means a straight-chain hydrocarbon radical having one or more triple bonds and from 2 to 10 carbon atoms; cycloalkyl, alone or in combination, is a saturated or partially saturated monocyclic, bicyclic or tricyclic hydrocarbon ring optionally benzo-fused containing from 3 to 8 carbon atoms; aryl, alone or in combination, means a phenyl or naphthyl radical optionally substituted with alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl carboxy, alkoxycarbonyl, cycloalkyl, heterocyclo, alkanoylamino, amido, amidino, alkoxycarbonylamino, N-alkylamidino, alkylamino, dialkylamino, N-alkylamido, N,N-dialkylamido, or aralkoxycarbonylamino radicals, heterocyclo, alone or in combination, means a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle having one or more nitrogen, oxygen or sulphur heteroatoms, which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo aryl, aralkyl heteroaryl, heteroaralkyl, amidino, N-alkylamidino, alkoxycarbonylamino and alkylsulfonylamino radicals, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, heteroaralkyl, phenyl or phenylalkyl radicals, or on a tertiary nitrogen atom by oxido radical; and heteroaryl, alone or in combination, means an aromatic heterocyclyl radical which is optionally substituted as defined above with respect to the definition of heterocyclo.