AR043941A1 - DERIVATIVES OF QUINOLINES 4-SUBSTITUTES, THEIR PREPARATION PROCEDURES AND INTERMEDIATES AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM - Google Patents

Abstract

This refers to quinoline derivatives 4-substituted process and pharmaceutical composition that composes it. Claim 1: A 4-substituted quinoline derivative, characterized in that it responds to the general formula (1), in which: X1, X2, X3, X4 and X5 respectively represent> C-R'1 to> CR'5, or well one at most among them represents a nitrogen atom; R1, R'1, R'2, R'3, R'4 and R'5 are the same or different and represent a hydrogen or halogen atom or an alkyl, cycloalkyl, phenyl, phenylthio, heteroaryl or heteroarylthio mono- radical or di-cyclic, OH, SH, alkyloxy, difluoromethoxy, trifluoromethoxy, alkylthio, trifluoromethylthio, cycloalkyloxy, cycloalkylthio, acyl, acyloxy, acylthio, cyano, carboxy, alkyloxy, alkyloxycarbonyl, cycloalkyloxycarbonyl, nitro or -NRaR queb -NRaRb--CRRR -B Ra and Rb may represent hydrogen, alkyl, cycloalkyl, phenyl, mono- or di-cyclic heteroaryl or Ra and Rb together with the nitrogen atom to which a 5 or 6 link heterocycle is attached which may optionally contain another heteroatom chosen from O, S or N and bearing a mono- or bi-cyclic alkyl, phenyl or heteroaryl substituent on the nitrogen atom, or, where appropriate, whose sulfur atom is oxidized to the sulfinyl or sulfonyl state), or represent a substituted methylene radical co n fluorine, hydroxy, alkyloxy, alkylthio, cycloalkyloxy, cycloalkylthio, phenyl, mono- or bi-cyclic heteroaryl, carboxy, alkyloxycarbonyl, cycloalkyloxycarbonyl, -NRaRb or -CONRaRb for which Ra and Rb are defined as above; Or they represent phenoxy, heterocyclyloxy, benzyloxy, heterocyclylmethyloxy, or R1 can also represent difluoromethoxy or a radical of structure -CmF2m + 1, -SCmF2m + 1 or -OcmF2 + 1 for which m is an integer of 1 6 or R '5 may also represent trifluoroacetyl; m is equal to 1, 2 or 3; n is equal to 0, 1 or 2; Y represents a group CHR, CO, CROH, CRNH2, CRF or CF2, where R is a hydrogen atom or a (C1-6) alkyl radical; Z represents a CH2 group, or Z represents an oxygen atom, a sulfur atom, an SO group or an SO2 group and, where appropriate, n is equal to 2; R2 represents a radical -CO2R, -CH2CO2R, -CH2-CH2CO2R, -CH2OH or -CH2-CH2OH, where R is as defined above; R3 represents a phenyl, heteroaryl, mono- or bi-cyclic radical, alk-Ro3 for which alk is an alkylene radical and Ro3 represents hydrogen, halogen, hydroxy, alkyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, cycloalkyl, cycloalkyloxy , cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylamino, N-cycloalkyl, N-alkyl-amino, -N- (cycloalkyl) 2, acyl, cycloalkylcarbonyl, phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylamino, N-alkyl-N-alkyl -amino, N-cycloalkyl-N-phenyl-amino, -N- (phenyl) 2, phenylalkylloxy, phenylalkylthio, phenylalkyl sulfyl, phenylalkyl sulfonyl, phenylalkyl amino, N-alkyl-N-phenyl-aminoalkyl, N-cycloalkyl-N-phenylalkyl-amino , benzoyl, mono- or bi-cyclic heteroaryl, heteroaryloxy, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylamino, N-alkyl-N-heteroaryl-amino, N-cycloalkyl-N-heteroaryl-amino, heteroarylcarbonyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl ilalkylthio, heteroarylalkylsulfinyl, heteroarylalkyl sulfonyl, heteroarylalkylamino, N-alkyl-N-heteroaryl-amino-alkyl, N-cycloalkyl-N-heteroaryl-aminoalkyl (the heteroaryl parts mentioned above are mono- or bi-cyclic), carboxy, alkyloxycarbonyl -NRaRb or -CO-NRaRb for which Ra and Rb respectively represent hydrogen, alkyl, cycloalkyl, phenyl, heteroaryl, mono- or bi-cyclic, or one of Ra or Rb represents hydroxy, alkyloxy, cycloalkyloxy, or Ra and Rb form together with the nitrogen atom to which a 5- to 6-stage heteroaryl is attached, which may optionally contain another heteroatom chosen from O, S and N and which, if appropriate, carries a mono- or bi-cyclic alkyl, phenyl or heteroaryl substituent on the nitrogen atom or, where appropriate, whose sulfur atom is oxidized to the sulfinyl sulfonyl state, or Ro3 represents -CR'b = CR'c-R'a for which R'a represents phenyl, phenylalkyl, heteroaryl or heteroarylalkyl whose p art heteroaryl is mono- or bi-cyclic, phenoxy, phenylthio, fenilsulfinilalquilo, fenilsulfonilalquilo, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, hetroarilaminoalquilo, N-alkyl-N-heteroaryl-aminoalkyl , heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, (the parts of heteroaryl mentioned above are mono- or bi-cyclic), phenylthio, phenylsulfinyl, phenylsulfonyl, and for which R'b and R'c represent hydrogen, alkyl or cycloalkyl, or Ro3 represents a radical -C = C-Rd for which Rd is alkyl, phenyl, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenyl-aminoalkyl, mono- or bi-cyclic heteroaryl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, heteroarylaminoalkyl , N-alkyl-N-heteroaryl-aminoalkyl (the heteroaryl parts mentioned above are mono- or bi-cyclic aromatic) or Ro3 represents a radical, -CF2-phenyl or -CF2-mono- or bi-cyclic heteroaryl, it being understood that the above-mentioned phenyl, benzyl, benzoyl or heteroaryl radicals or parts are optionally substituted in the cycle with 1 to 4 substituents chosen from hydrogen , hydroxy, alkyl, alkyloxy, alkyloxyalkyl, halogenoalkyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, carboxy, alkoxycarbonyl, cyano, alkylamino, -NRaRb for Ra and Rb are defined as above, phenyl, hydroxyalkyl, alkylthioalkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylsilylalkyl, alkyl it is understood that the alkyl or acyl radicals and parts contain (unless special mention) C1-10 in a linear or branched chain and that the C3-6 cycloalkyl radicals, in their enantiomeric or diastereomeric forms or mixtures of these forms, and / or where appropriate in syn or anti form or their mixtures, as well as their salts.