ANALOGUES OF N-ACETYLARDEEMIN, METHOD OF PREPARATION AND USES THEREOF

摘要

The present invention provides a compound having structure (I) wherein R1, R6 and R7 are independently hydrogen, OH, NH2. SH, halogen, C1-C9 linear or branched chain alkyl, alkylmercapto, alkylamino, dialkylamino, alkoxy, phenyl, etc; wherein R0 and R2 are independently hydrogen, OH, linear or branched chain alkyl, -CR3R3-CH(O)CH2, -CR3R3-CH2CH3, -CR3R3- CH2CH2OH, -CR3R3-CH(OH)R4 or -CR3R3-CH-CHR4, wherein R3 and R4 are independently hydrogen, halogen, C1-C9 linear or branched chain alkyl , phenyl, etc; wherein R5 is hydrogen, C1-C9 linear or branched chain alkyl, phenyl, etc; an wherein R8 is hydrogen C1-C9 linear or branched chain acyl, benzoyl, etc; with the proviso that (a) when R2 is -CR3R3-CH(O)CH2, -CR3R3-CH2CH3, -CR3R3-CH2CH2OH, -CR3R3-CH(OH)R4 or -CR3R3-CH=CHR4, then R0 is hydrogen; (b) when R0 is -CR3R3-CH(O)CH2, -CR3R3-CH2CH3, -CR3R3-CH2CH2OH, -CR3R3- CH(OH)R4 or -CR3R3-CH=CHR4, then R2 is OH; and (c) when (i) R0 or R2 is -CR3R3-CH=CHR4, (ii) R3 and R5 are CH3 and (iii ) R4 is hydrogen, then R1, R6 and R7 are not all hydrogen. Also provided are related compounds and compositions, and methods of inhibiting the growth of multidrug resistant cells by means of MDR reversal, collateral sensitivity and quantitative synergism.