Patent FR-2816618-A1 (FR)
Title: New 4-(quinolin-4-yl-alkyl)-piperidine derivatives, are low toxicity antimicrobial agents effective against Gram positive and Gram negative bacterial infections
Inventor: BACQUE ERIC
IPC: C07D409/14
Filed: 2000-11-15
Abstract: 1,4-Disubstituted 4-(quinolin-4-yl-alkyl)-piperidine derivatives (I) are new.  Piperidine derivatives of formula (I), their enantiomers, diastereomers and mixtures, syn- or anti-isomers and salts, are new. X1 - X5  = CR or N, provided that only one may be N;  R, R1  = H, halo, alkyl, cycloalkyl, Ph, SPh, Het, -S-Het, OH, alkoxy, OCF3, alkylthio, SCF3, cycloalkoxy, cycloalkylthio, CN, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NRaRb, CONRaRb, CH2T, OPh, heterocyclyloxy, benzyloxy or heterocyclylmethoxy; or R1 may also be 1-6C perfluoroalkyl, 1-6C perfluoroalkoxy or 1-6C perfluoroalkylthio; or R in the X5 position may also be COCF3;  Het  = mono- or bicyclic aromatic heterocyclyl;  Ra, Rb  = H, alkyl, cycloalkyl, phenyl or Het; or NRaRb  = 5- or 6-membered heterocyclyl, optionally containing another O, S, SO, SO2 or NQ heteroatom;  Q  = H, Ph or Het;  T  = F, OH, alkoxy, alkylthio, cycloalkoxy, cycloalkylthio, Het, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NRaRb or CONRaRb;  R2  = COOH, alkoxycarbonyl, cycloalkoxycarbonyl, CN, COOH, SO3H, CONR'aR'b, CH2OH, -U-V, CF2Rc, CMe2-Rc, CORc, CH(OH)Rc, -C(cycloalkyl)-Rc or -CH=CH-Rc;  R'a, R'b  = as Ra, Rb, except that one of R'a, R'b may also be OH, alkoxy or cycloalkoxy; or NR'aR'b  = heterocycle as defined for NRaRb;  U  = 1-2C alkylene;  V  = COOH, alkoxycarbonyl, cycloalkoxycarbonyl, CN, SO3H or CONR'aR'b;  Rc  = COOH, alkoxycarbonyl, cycloalkoxycarbonyl or CONR'aR'b;  R3  = Ph, Het or alkyl (optionally substituted by R'3);  R'3  = halo, OH, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, mono- or dialkylamino, cycloalkyl, cycloalkoxy, cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, mono- or dicycloalkylamino, N-alkyl-N-cycloalkylamino, acyl, cycloalkylcarbonyl, Ph, OPh, SPh, SOPh, SO2Ph, NHPh, NPh2, N-alkyl-N-phenylamino, N-cycloalkyl-N-phenylamino, phenylalkoxy, phenylalkylthio, phenylalkylsulfinyl, phenylalkylsulfonyl, phenylalkylamino, N-alkyl-N-phenylalkylamino, N-cycloalkyl-N-phenylalkylamino, benzoyl, -O-Het, -S-Het, -SO-Het, -SO2-Het, -NH-Het, N-alkyl-N-(Het)-amino, N-cycloalkyl-N-(Het)-amino, -CO-Het, Het-alkoxy, Het-alkylthio, Het-alkylsulfinyl, Het-alkylsulfonyl, Het-alkylamino, N-alkyl-N-(Het-alkyl)-amino, N-cycloalkyl-N-(Het-alkyl)-amino, COOH, alkoxycarbonyl, NR'aR'b, CONR'aR'b, -C(R''b)=C(R'c)-R''a, -CC-Rd, -CF2-phenyl or -CF2-Het;  R''a  = Ph, phenylalkyl, Het, Het-alkyl, phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, Het-O-alkyl, Het-S-alkyl, Het-SO-alkyl, Het-SO2-alkyl, Het-NH-alkyl, N-alkyl-N-(Het)-amino, -S-Het, -SO-Het, -SO2-Het, SPh, SOPh or SO2Ph; R''b, R'c  = H, alkyl or cycloalkyl;  Rd  = alkyl, Ph, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenylaminoalkyl, Het, Het-alkyl, Het-O-alkyl, Het-S-alkyl, Het-NH-alkyl or N-alkyl-N-(Het)-aminoalkyl;  Y  = -CH(Re)-, CF2, CO C(=NOH), alkoxyiminomethylene, cycloalkoxyiminomethylene or 3-6C cycloalkylidene;  Re  = H, F, OH, alkoxy, cycloalkoxy, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NQaQb or CONQaQb;  Qa, Qb  = as R'a, R'b; or one is H and the other is alkoxycarbonyl, acyl, cycloalkoxycarbonyl, -CO-Ph or -CO-Het; and n  = 0-4;  phenyl and heterocyclyl moieties are optionally substituted by 1-4 of halo, OH, alkyl, alkoxy, alkoxyalkyl, haloalkyl, CF3, OCF3 SCF3, COOH, alkoxycarbony, CN, alkylamino, NR'aR'b, Ph, hydroxyalkyl, alkylthioalkyl, alkylsulfonylalkyl or alkylsulfonylalkyl; alkyl or acyl moieties have 1-10C (unless specified otherwise); cycloalkyl moieties have 3-6C.  An Independent claim is included for the preparation of (I).