Compositions and methods of the use thereof achiral analogues of CC-1065 and the duocarmycins
AssigneeTaiho Pharmaceutical Co., Ltd.
InventorMoses Lee
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Abstract
The present invention relates to novel achiral seco-analogues of DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class I, II, III, IV and V: wherein X is a good leaving group, such as a chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (Cl) or an achiral seco-duocarmycin with specific sequences of DNA.
Claims14
A compound of the formula
- wherein:
- X is a good leaving group,
- R1 is a suitable minor groove binding agent selected from the group consisting of t-butoxy, benzyloxy, 9-fluorenylmethyloxy, and groups A, B, C, D, E, F, G, H, I, J, and K as shown in the following formulas,
- R2 and R3 are selected from the group consisting of hydrogen and (C1-C6) alkyl groups,
- R4 and R5 are selected from the group consisting of hydrogen atoms, (C1-C6) alkyl groups, trifluoromethyl moieties, and C1-C6 alkyloxycarbonyl groups,
- R is selected from the group consisting of benzyl, benzyloxycarbonyl, hydrogen atom, 4-nitrobenzyloxycarbonyl, and N′-methylpiperazinyl-N-carbonyl.
Dependencies are inferred from the claim text.