Butitaxel analogues: synthesis and structure-activity relationships.
Basic Information
ID: ALA1130165
Journal: J Med Chem
Title: Butitaxel analogues: synthesis and structure-activity relationships.
Authors: Ali SM, Hoemann MZ, Aubé J, Georg GI, Mitscher LA, Jayasinghe LR.
Abstract: N-Acyl analogues 8, 9, and 12-26 of butitaxel (3) were prepared in one or two steps from amines 5 and 6 through Schotten-Baumann acylation. Seventeen novel analogues, consisting of aliphatic carbamates, alicyclic amides, and heteroaromatic amides, were synthesized. They were evaluated for their in vitro ability to stimulate the formation of microtubules, their cytotoxicity toward B16 melanoma cells, and their solubility in water. The most potent analogue found in this study was N-debenzoyl-N-(2-thenoyl)butitaxel (20), possessing ca. 2-fold better tubulin assembly properties and cytotoxic activity against B16 melanoma cells than paclitaxel. Compound 20 was ca. 25 times more water soluble than paclitaxel.
CiteXplore: 9003522
DOI: 10.1021/jm960505t
Patent ID: ┄