| 摘要 |
The invention provides novel cryptophycin compounds which can be useful for disrupting the microtubulin system, as antineoplastic agents, and for the treatment of cancer. The invention further provides a formulation for administering the novel cryptophycin compounds. The compounds are of the formula <CHEM> wherein Ar is phenyl or any simple unsubstituted or substituted aromatic or heteroaromatic group; R<1> is halogen, SH, amino, monoalkylamino, dialkylamino, trialkylammonium, alkylthio, dialkylsulfonium, sulfate, or phosphate; R<2> is OH or SH; or R<1> and R<2> may be taken together to form an epoxide ring, and aziridine ring, an episulfide ring, a sulfate ring, or monoalkylphosphate ring; or R<1> and R<2> may be taken together to form a second bond between C18 and C19; R<3> is a lower alkyl group; R<4> is H; R<5> is H; R<4> and R<5> may be taken together to form a second bond between C13 and C14; R<6> is benzyl, hydroxybenzyl, alkoxybenzyl, halohydroxybenzyl, dihalohydroxybenzyl, haloalkoxybenzyl, or dihaloalkoxybenzyl group; R<7> is H or a lower alkyl group; R<8> is H or a lower alkyl group; or R<7> and R<8> may optionally be taken together to form a cyclopropyl ring; R<9> is selected from the group consisting of H, a lower alkyl group, (C1-C3) alkylaryl, and aryl; R<10> is selected from the group consisting of H, a lower alkyl group, (C1-C3) alkylaryl, and aryl; R<11> is H; simple alkyl; phenyl, substituted phenyl, benzyl, substituted benzyl; X is O, NH or alkylamino; Y is C, O, NH, S, SO, SO2 or alkylamino; and a pharmaceutically acceptable salt or solvate thereof. |
