Nitrobenzyl mustard quaternary salts and their use as hypoxia-selective cytotoxic agents

摘要

PCT No. PCT/NZ94/00046 Sec. 371 Date Sep. 27, 1995 Sec. 102(e) Date Sep. 27, 1995 PCT Filed May 24, 1994 PCT Pub. No. WO94/27954 PCT Pub. Date Dec. 8, 1994Nitrobenzyl mustard quaternary salts of formula (I), <IMAGE> (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 other 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 H-Cl or Br, Q=Me, and X=CH2- then Ar NOTEQUAL 2-nitrophenyl or 4-nitrophenyl.