NITROGEN MUSTARD COMPOUNDS AND PRODRUGS THEREFOR

摘要

This invention pertains to nitrogen mustard compounds (Formula (II)) and prodrugs therefor (Formula (I)), methods for their preparation, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in therapy and treatment, for example, of cancer, wherein: R<1> and R<2> are independently -Cl, -Br, -I, -OSO2CH3, or -OSO2Ph; R<1a>, R<2a>, R<1b>, and R<2b> are independently -H, a C1-4alkyl group, or a C1-4haloalkyl group; R<3> is -F, -Cl, -Br, -I, -OCHF2, -CCH, -OCF3, -CH3, -CF3, -SF5, -SCF3, or -CF2CF3; R<4> is -H or as defined for R<3>; R<5> is -H or -F; R<7> is -H, -C(CH3)3, or -CH2-CH=CH2; Z is -CH2-T-W; T is -CH2-, -O-, -S-, -(S=O)-, or -(SO2)-; W is one of: (1) -COOH; (2) -(C=O)OR<8>; (3) -(C=O)NR<9>R<9>; (4) -SO2NHR<10>; (5) -SO2OR<11>; (6) -PO3R<11>R<11>; (7) a tetrazol-5-yl group; (8) -CONH-SO2R<12>; and, (9) -M-Het.