Use of pyrrolidine-2,5-dione and piperidine-2,6-dione derivatives as mycobacterial (especially tuberculosis) inhibitors

摘要

The compound of formula (I), useful for the treatment of mycobacterial diseases, where in the compound of formula (I): x is 0 or 1; R1 is H, or an alkyl or myrtanyl group, or a phenyl or benzyl group optionally substituted in the aromatic ring by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl, or a group (CH2)yCONH-R5 where y is an integer from 1 to 6 and R5 represents a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl; and either R2 is H or an alkyl group, or R2 together with R3 represents a carbon-carbon single bond provided that x is 0, or R2 together with R4 represents a group =CH2, R3 is H or is linked to R2 as defined above, and R4 is H or an alkyl group; or an alkylamino group optionally substituted by a dialkylamino substituent group; or an anilino group substituted in the aromatic ring by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl; or a group -SCH2CH2OH, -SCH2CH2NH2, -SCH2CH2(NH2)CO2H or -SCH2CH2NHCO-R6 where R6 represents an alkyl or cycloalkyl group, or a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl; or R4 is linked to R2 as defined above; or R2, R3 and R4 together represent a phenyl group; with the provisos that: (i) R1, R2, R3 and R4 do not each simultaneously represent H, (ii) when x is 0, R1 represents a 4-fluorophenyl group and R4 represents H, then R2 and R3 do not together represent a carbon-carbon single bond, (iii) when x is 0, R1 represents a 4-fluorophenyl group and R2 and R3 both represent H, then R4 does not represent an anilino, 4-chloroanilino, 2,6-dichloroanilino, 3,4-dichloroanilino, 2,5-dichloroanilino, 3-chloro-4-fluoroanilino or 4-fluoroanilino group.