著者

尾崎 庄一郎 渡辺 裕 / 長瀬 敏雄 小笠原 富夫 古川 弘幸 上村 敦彦 石川 勝敏 / / 徳善 令子 AKIO HOSHI MASAAKI IIGO REIKO TOKUZEN

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.1, pp.150-157, 1986-01-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

15 23

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With the aim of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, α-alkoxyalkyl groups were introduced at the 1-, 3-and 1, 3-positions of 1. Alkoxyalkylation can be effected by four methods : (i) reaction of 1-alkoxyalkyl chloride (2) with 1, (ii) reaction of acetal with 2, 4-bis (trimethylsiloxy)-5-fluoropy-rimidine, (iii) addition reaction of α-unsaturated ether with 1, (iv) aminolysis of 1-alkylthio-carbonyl-3-(1-alkoxyalkyl)-5-fluorouracil. The toxicity of the products was less than that of 1, and some of these compounds showed moderate antitumor activity against L-1210 leukemia.

著者

長瀬 敏雄

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.57, no.10, pp.888-897, 1999 (Released:2009-11-16)

参考文献数

40

被引用文献数

1 1

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Medicinal chemistry efforts on optimization of the endothelin receptor antagonistic natural products toward highly potent and selective ETA, ETB or ETA/B dual receptor antagonists are summarized. In order to get adequate biological tools for elucidating physiological and/or pathophysiological roles of endothelin as well as to identify highly potent antagonists possessing appropriate profiles, liquid phase and solid phase peptide synthesis, and their modification have been carried out. During these efforts, we have realized physiological roles of endothelin and its receptors, and have confirmed drug discovery values of its receptor antagonists as clinical drugs to modulate various kinds of disease.