NITROBENZYL MUSTARD QUATERNARY SALTS AND THEIR USE AS HYPOXIA-SELECTIVE CYTOTOXIC AGENTS

摘要

Nitrobenzyl mustard quaternary salts of formula (I), and the pharmaceutically acceptable salts thereof, process for their manufacture and their chemotherapeutic use as hypoxia selective cytotoxic agents. Wherein, X represents a linker chain -CR1R2- or CR1=CR2- (where R1 and R2 are separately H, lower alkyl, phenyl or nitrophenyl; Y is halogen or OSO2R; Q is lower alkyl (optionaly substituted with alkyl and/or ether groups and containing up to 6 carbons) or nitrophenyl; Ar represents a mono- or bicyclic aromatic unit, R is lower alkyl optionally substituted with alkyl and/or ether groups, and may contain up to eight carbon atoms. Z represents one or more of the groups NO2, SO2R, CONHR, R, OR, SR, CF3 and aza (ring -CH= replaced by -N=); with the proviso that when Y=Cl or Br, Q=Me, and X=-CH2- then Ar NOTEQUAL 2-nitrophenyl or 4-nitrophenyl.