ChemInform Abstract: Synthesis and Structure-Activity Relationships of Novel 2′,2′-Difluoro Analogues of Docetaxel

Autor:	Kouichi Uoto, Shin Iimura, Takashi Ishiyama, Satoru Ohsuki, Hirofumi Terasawa, Haruhiro Takenoshita, Tsunehiko Soga, Ikuo Mitsui, Y. Hirota
Rok vydání:	2010
Předmět:	Terpene Human tumor Mouse Leukemia Docetaxel Stereochemistry Cell culture Chemistry Side chain medicine Alpha (ethology) General Medicine Cytotoxicity medicine.drug
Zdroj:	ChemInform. 29
ISSN:	1522-2667 0931-7597
Popis:	To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha, alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::086fec225b515a690c2296da4f4795e2 https://doi.org/10.1002/chin.199818200 Zobrazit plný text záznamu Plný text