Patent FR-2858324-A1 (FR)
Title: Composition used for treating microbial infections, effective particularly against rifampicin-resistant bacteria, contain new or known 5-(heterocyclylmethylene)-thiazolidine derivatives
Inventor: LEONETTI JEAN PAUL
IPC: C07D277/20
Filed: 2003-07-30
Abstract: Composition contains 3-substituted 5-(heterocyclylmethylene)-thiazolidine-2,4-one derivatives (including thione and/or imine analogs) (I) as active agents. Compositions containsa at least one thiazolidine derivative of formula (I) (in E- or Z-form or as an E/Z-mixture and including thione and/or imine analogs)) as an active agent, together with a carrier. [Image] X, Y : O, S, NH or NR; R : 1-5C alkyl (optionally substituted (os) by N or O); Ra1-16C alkyl or 2-16C alkenyl (both os by halo, CHO, COOH, CN, COOM, SR1, SOR1, SO2R1, SO2, SO2OH, SO3M, CF3, CHF2, (CF2)mCF3 or (CF2)mCF3) or 5- or 6-membered heterocyclyl (specifically 2-furanyl, 2-tetrahydrofuranyl, morpholino, 3-pyridinyl, N-(R6)-piperazino), 2-oxo-pyrrolidino, 4-hydroxy-2-oxo-pyrrolidino, 2-carboxypyrroldino or 2-carboxy-4-hydroxypyrrolidino); M : alkali(ne earth) metal (specifically Na, Ca, Mg, Al (sic), Zn (sic) or Li); R1H or 1-16C alkyl (specifically Me, Et or tert. butyl); m : 1-3; A : 5- or 6-membered heterocyclyl containing at least one of N, O, S, P, Si and/or Se as heteroatoms and optionally fused with another 4-7 membered ring (optionally containing heteroatom(s) as above) (preferably thiophene, pyrrole, 2H-pyrrole, 2H- or 3H-pyrroline, pyrrolidine, oxazole, thiazole, imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-, 1,2,4- or 1,3,4-oxadiazole, 1,2,3-, 1,2,4- or 1,3,4-triazole, 1,2,4- or 1,3,4-thiadiazole, 2H- or 4H-pyran, 3,4- or 3,6-dihydro-2H-pyran, tetrahydropyran, pyridine, 2,3-. 1,2- or 1,4-dihydropyridine, 1,2,3,4-, 1,2,3,6- or 2,3,4,5-tetrahydropyridine, piperidine, 1,4-dioxan, 1,4-dithian, morpholine, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, 1,3,5-, 1,2,3- or 1,24-triazine or purine), all os (specifically by one or more groups Q); Q : 1-16C alkyl or 6-30C aryl (preferably phenyl) (both os by one or more groups, specifically by halo (preferably Cl, Br or F), COOR1, OR1, CF3, NO2, SO2NH2, COMe or CN), heterocyclyl as defined for A, or halo, OR1a, COOR2, CN, COOM, SR1, SOR1, SO2R1, SO2, SO2OH, SO3M, NR3R4, NO2, CF3, CHF2, (CF2)mCF3 or (CF2)mCF3; R1aR1, or 2-16C alkenyl, 2-16C alkynyl, 5C, 6C, 9C, 10C or 12C aryl, 5C, 6C, 9C, 10C or 12C heteroaryl (containing at least one N, O or S), 4-8C cycloalkyl or 4-8C cycloalkenyl; R2R1 or 2-16C alkenyl or 2-16C alkynyl; R3, R4H, 1-16C alkyl, 2-16C alkenyl, 2-16C alkynyl, 5C, 6C, 9C, 10C or 12C aryl, 5C, 6C, 9C, 10C or 12C heteroaryl (containing at least one N, O or S), 4-8C cycloalkyl or 4-8C cycloalkenyl, or R3 + R44-6 membered ring. An independent claim is included for (I; A = A') as new compounds. A' : 1,2,4- or 1,3,4-oxadiazole, 1,2,4- or 1,3,4-thiadiazole, 1,2,4- or 1,3,4-triazole, imidazole, oxazole or thiazole. ACTIVITY : Antibacterial; Tuberculostatic. In tests, (Z)-3-(furan-2-ylmethyl)-5-(5-(3-trifluoromethylphenyl)-furan-2-ylmethylene)-2-thioxothiazolidin-4-one (Ia) exhibited IC50 values of 1.17 mu g/ml against Staphylococcus aureus CIP 76.25, 0.58 mu g/ml against Streptococcus epidermidis CIP 68.21 and 1.17 mu g/ml against Bacteriodes megaterium, and showed no cytotoxicity towards Chinese hamster ovary cells at concentrations up to 200 mu g/ml. MECHANISM OF ACTION : Bacterial RNA polymerase transcription inhibitor.