Conformationally restrained epothilone analogues as anti-leukemic agents
A method for synthesizing anti-leukemic epothilone analogues includes rigidifying a region between the macrolactone ring and the aromatic side-chain. The anti-leukemic compositions are non-naturally occurring epothilone analogue that are rigidified between the macrolactone ring and the aromatic side-chain.
1. A composition comprising at least one epothilone analogue selected from the group consisting of:
an epothilone analogue represented by the following formula (1a) or a pharmaceutically acceptable salt, thereof:
an epothilone analogue represented by the following formula (1b) or a pharmaceutically acceptable salt, thereof:
a combination thereof.
2. The composition of claim 1 , which comprises at least 50 wt. % of at least one epothilone analogue of claim 1 , based on the total weight of the composition.
3. The composition of claim 1 , further comprising a therapeutically effective amount of at least one epothilone analogue of claim 1 ; and a pharmaceutically acceptable carrier.
4. An epothilone analogue represented by the following general formula (1) or a pharmaceutically acceptable salt, thereof:
wherein:
R is a hydrogen atom or a methyl group; and
X is a carbon atom or a nitrogen atom.
5. The epothilone analogue according to claim 4 , which is represented by the following formula (1a) or a pharmaceutically acceptable salt, thereof:
6. The epothilone analogue according to claim 4 , which is represented by the following formula (1b) or a pharmaceutically acceptable salt, thereof: