155399-27-2Relevant articles and documents
No auxiliary, no byproduct strategy for water-soluble prodrugs of taxoids: Scope and limitation of O-N intramolecular acyl and acyloxy migration reactions
Skwarczynski, Mariusz,Sohma, Youhei,Noguchi, Mayo,Kimura, Maiko,Hayashi, Yoshio,Hamada, Yoshio,Kimura, Tooru,Kiso, Yoshiaki
, p. 2655 - 2666 (2007/10/03)
Since numerous new taxoids active against multidrug resistant (MDR) tumors have been developed and their poor water-solubility is a very real problem in intravenous administration, we have designed and synthesized a series of novel water-soluble taxoid prodrugs (isotaxoids). These prodrugs, a 2′-O-isoform of taxoids, showed promising results with higher water solubility (0.8-1.1 mg/mL) and proper kinetics for parent drug release by a simple pH-dependent chemical mechanism via O-N intramolecular acyl migration. No additional functional auxiliaries are released during the conversion to parent drugs, which would be an advantage in toxicology and general pharmacology, and the cost for the evaluations of auxiliary units in these fields could be saved in prodrug development. In addition, we demonstrate for the first time the successful application of the O-N intramolecular acyloxy migration reaction in the prodrug design, with the exception of the tert-butyloxycarbonyl group, and that this reaction can be provided with no organic solvent and no side products.
Synthesis of a photoaffinity taxol analogue and its use in labeling tubulin
Dasgupta,Park,Harriman,Georg,Himes
, p. 2976 - 2980 (2007/10/02)
A photoaffinity analogue of taxol, N-([3,5-3H]-4-azidobenzoyl)-N- debenzoyltaxol (7), was synthesized and used to photolabel microtubules. Approximately 20% of the noncovalently bound analogue becomes covalently bound upon irradiation at 300 nm. Incorporated label was stable to a 50% ethanol solution and sodium dodecyl sulfate. About 80% of the incorporated label was found in the β-subunit and 20% in the α-subunit. Incorporation did not occur into unpolymerized tubulin, consistent with the fact that taxol binds only to polymerized tubulin, and was decreased by the presence of taxol. Little or no nonspecific labeling occurs. This analogue is currently being used to identify taxol binding site(s) on tubulin.