Patent EP-1695964-A1 (EP)
Inventor: BACQE ERIC
IPC: A61P31/00
Filed: 2001-11-14
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. [Image] X 1- X 5CR or N, provided that only one may be N; R, R 1H, halo, alkyl, cycloalkyl, Ph, SPh, Het, -S-Het, OH, alkoxy, OCF 3, alkylthio, SCF 3, cycloalkoxy, cycloalkylthio, CN, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NR aR b, CONR aR b, CH 2T, OPh, heterocyclyloxy, benzyloxy or heterocyclylmethoxy; or R 1may also be 1-6C perfluoroalkyl, 1-6C perfluoroalkoxy or 1-6C perfluoroalkylthio; or R in the X 5position may also be COCF 3; Het : mono- or bicyclic aromatic heterocyclyl; R a, R bH, alkyl, cycloalkyl, phenyl or Het; or NR aR b5- or 6-membered heterocyclyl, optionally containing another O, S, SO, SO 2or NQ heteroatom; Q : H, Ph or Het; T : F, OH, alkoxy, alkylthio, cycloalkoxy, cycloalkylthio, Het, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NR aR bor CONR aR b; R 2COOH, alkoxycarbonyl, cycloalkoxycarbonyl, CN, COOH, SO 3H, CONR' aR' b, CH 2OH, -U-V, CF 2R c, CMe 2-R c, COR c, CH(OH)R c, -C(cycloalkyl)-R cor -CH=CH-R c; R' a, R' bas R a, R b, except that one of R' a, R' bmay also be OH, alkoxy or cycloalkoxy; or NR' aR' bheterocycle as defined for NR aR b; U : 1-2C alkylene; V : COOH, alkoxycarbonyl, cycloalkoxycarbonyl, CN, SO 3H or CONR' aR' b; R cCOOH, alkoxycarbonyl, cycloalkoxycarbonyl or CONR' aR' b; R 3Ph, Het or alkyl (optionally substituted by R' 3); R' 3halo, 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, SO 2Ph, NHPh, NPh 2, 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, -SO 2-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-R d, -CF 2-phenyl or -CF 2-Het; R'' aPh, phenylalkyl, Het, Het-alkyl, phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, Het-O-alkyl, Het-S-alkyl, Het-SO-alkyl, Het-SO 2-alkyl, Het-NH-alkyl, N-alkyl-N-(Het)-amino, -S-Het, -SO-Het, -SO 2-Het, SPh, SOPh or SO 2Ph; R'' b, R' cH, alkyl or cycloalkyl; R dalkyl, 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(R e)-, CF 2, CO C(=NOH), alkoxyiminomethylene, cycloalkoxyiminomethylene or 3-6C cycloalkylidene; R eH, F, OH, alkoxy, cycloalkoxy, COOH, alkoxycarbonyl, cycloalkoxycarbonyl, NQ aQ bor CONQ aQ b; Q a, Q bas 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, CF 3, OCF 3SCF 3, 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). ACTIVITY : Antibacterial. (I) show activity in vitro against methicillin-resistant Staphylococcus aureusAS5155 at 0.03-4 Microg/ml, Streptococcus pneumoniae6254-01 at 0.03-8 Microg/ml and Moraxella catarrhalisIPA 152 at 0.12-64 Microg/ml, and in vivo against Staphylococcus aureusIP8203 infections in mice at 18-150 mg/ml s.c. (DC 50). No specific results for individual compounds are given in the source material. MECHANISM OF ACTION : None given.