SUBSTITUTED QUINOLINES AND THEIR USE AS MYCOBACTERIAL INHIBITORS

• Main Authors: GUILLEMONT, JEROME EMILE GEORGES, PASQUIER, ELISABETH THERESE JEANNE
• Format: Patent
• Language: English; French
• Published: 04.08.2005
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to novel substituted quinoline derivatives according to the general formula (Ia) or the general formula (Ib) salts, quaternary amines, stereochemically isomeric forms, tautomeric forms and N~- oxide forms thereof, wherein R1 is hydrogen, halo, haloalkyl, cyano, hydroxy , Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl ; p is 1, 2, 3 or 4 ; R2 is hydrogen, hydroxy, thio, alkyloxy , alkyloxyalkyloxy, alkylthio, mono or di(alkyl)amino or a radical of formula (Ic);R3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl; R4 is hydrogen, alkyl or benzyl; R5 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl ; or two vicinal R5 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl; r is 1, 2, 3, 4 or 5 ; R6 is hydrogen, alkyl, Ar or Het R7 is hydrogen or alkyl; R8 is oxo ; or R7 and R8 taken together form the radical - CH=CH-N=; Z is CH2 or C(=O). The claimed compounds are useful for the treatment of mycobacterial diseases, particular ly those diseases caused by pathogenic mycobacteria such as M. tuberculosis, M. bovis, M. avium, M. smegmatis and M. marinum. Also claimed is a pharmaceutic al composition containinga compound of the present invention, the use of the claimed compounds or compositions for the manufacture of a medicament for th e treatment of mycobacterial diseases and a process for preparing the claimed compounds.