Patent FR-2867472-A1 (FR)
Title: New 4-((piperidin-4-ylamino)-alkyl)-quinoline derivatives, useful as antibacterial agents e.g. for treatment of staphylococcal infections
Inventor: BIGOT ANTONY
IPC: C07D409/14
Filed: 2004-03-12
Abstract: 4-((1-Substituted piperidin-4-ylamino)-alkyl)-quinoline derivatives (I) are new. Quinoline derivatives of formula (I) (including enantiomers, diastereomers, syn/anti-forms and their mixtures) and their salts are new. X1 - X6C-R'1 - C-R'5 respectively, one of which may be replaced by N; R1, R'1 - R'5H, halo, alkyl, cycloalkyl, phenyl, Het, S-Het, OH, SH, alkoxy, OCHF2, OCF3, alkylthio, SCF3, cycloalkoxy, cycloalkylthio, acyl, acyloxy, acylthio, CN, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NO2, NRaRb, CONRaRb, -CH2Q, phenoxy, heterocyclyloxy, benzyloxy or heterocyclylmethoxy; or R1 may also be OCHF2, Rf, SRf or ORf; or R'5 may also be COCF3; Het : mono- or bicyclic heteroaryl; Ra, RbH, alkyl, cycloalkyl, phenyl or Het; or NRaRb5- or 6-membered heterocycle, optionally containing another O, S, N, N(alkyl), N(Ph), N(Het), SO or SO2 heteroatom); Q : F, OH, alkoxy, alkylthio, cycloalkoxy, cycloalkylthio, phenyl, Het, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NRaRb or CONRaRb; Rf1-6C perfluoroalkyl; m : 1 or 2; Y : CHR, CO, C(R)OH, C(R)NH2, C(R)f or CF2; R : H or 1-6C alkyl; R2COOR, CH2COOR, CH2CH2COOR, CONH2, CH2CONH2, CH2CH2CONH2, CH2OH, CH2CH2OH, CH2NH2, CH2CH2NH2 or (CH2)3NH2, R2 being in the 3- or 4-position; R3phenyl, Het or -alk-R03; alk : alkylene; R03H, halo, OH, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, mono- or dialkylamino, cycloalkyl, cycloalkoxy, cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, mono- or dicycloalkylamino, N-cycloalkyl-N-alkylamino, acyl, cycloalkylcarbonyl, phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, mono- or diphenylamino, N-alkyl-N-phenylamino, N-cycloalkyl-N-phenylamino, phenylalkoxy, phenylalkylthio, phenylalkylsulfinyl, phenylalkylsulfonyl, phenylalkylamino, N-alkyl-N-phenylaminoalkyl, N-cycloalkyl-N-phenylalkylamino, benzoyl, Het, O-Het, S-Het, SO-Het, SO2-Het, NH-Het, N-alkyl-N-Het-aminoalkyl, N-cycloalkyl-N-Het-aminoalkyl, COOH, alkoxycarbonyl, NR'aR'b, CONR'aR'b, -C(R''b)=C(R'c)-R''a, -CC-Rd, -CF2-Ph or -CH2-Het; R'a, R'bas for Ra, Rb, except that one of R'a and R'b may additionally be OH, alkoxy or cycloalkoxy; R''aphenyl, phenylalkyl, Het, Het-alkyl, phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, Het-O-alkyl, Het-S-alkyl, Het-S-alkyl, Het-SO-alkyl, Het-SO2-alkyl, Het-NH-alkyl, Het-N(alkyl)-alkyl, SHet, SOHet, SO2Het, phenylthio, phenylsulfinyl or phenylsulfonyl; R''b, RcH, alkyl or cycloalkyl; Rdalkyl, phenyl, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenylaminoalkyl, Het, Het-alkyl, Het-S-alkyl, Het-NH-alkyl or Het-N(alkyl)-alkyl; phenyl or heteroaryl moieties are optionally substituted by 1-4 of halo, OH, alkyl, alkoxy, alkoxyalkyl, haloalkyl, CF3, OCF3, SCF3, COOH, alkoxycarbonyl, CN, alkylamino, NRaRb, hydroxyalkyl, alkylthioalkyl, alkylsulfinylalkyl or alkylsulfonylalkyl; unless specified otherwise alkyl or acyl moieties have 1-10C and cycloalkyl moieties 3-6C. Independent claims are also included for: (1) Preparation of (I); and (2) New quinoline derivative intermediates of formula (II). [Image] ACTIVITY : Antibacterial. 1-(2-(2,5-Difluoro-phenylsulfanyl)-ethyl)-4-(2-(3-fluoro-6-methoxy-quinolin-4-yl)-2-hydroxyethylamino)-piperidine-3-carboxylic acid (Ia), diastereomers A, B, C or D, had MIC values (24 hours) in the range 0.5-2 mg/l against methicillin resistant Staphylococcus aureus strain AS 5155. MECHANISM OF ACTION : None given.