| Literature DB >> 15261301 |
Arie Zask1, Gary Birnberg, Katherine Cheung, Joshua Kaplan, Chuan Niu, Emily Norton, Ayako Yamashita, Carl Beyer, Girija Krishnamurthy, Lee M Greenberger, Frank Loganzo, Semiramis Ayral-Kaloustian.
Abstract
Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein. Amides derived from proline had potency comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols or its conversion to acidic heterocycles also gave potent analogs. Synthetic modifications of the carboxylic acid could be carried out selectively using a wide range of synthetic reagents. Proline analog 3 was found to be effective in a human xenograft model in athymic mice.Entities:
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Year: 2004 PMID： 15261301 DOI： 10.1016/j.bmcl.2004.05.005
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823