著者
MINEO SANEYOSHI MOTOKO INOMATA TERUAKI SEKINE AKIO HOSHI FUMIKO FUKUOKA
出版者
The Pharmaceutical Society of Japan
雑誌
Journal of Pharmacobio-Dynamics (ISSN:0386846X)
巻号頁・発行日
vol.1, no.3, pp.168-174, 1978 (Released:2008-02-21)
参考文献数
12
被引用文献数
6 6

Reaction of S-benzylthioisothiouronium hydrochloride with 6-mercaptopurine (1), 9-β-D-ribofuranosyl-6-mercaptopurine (2), 6-thioguanine (3) and 9-β-D-ribofuranosyl-6-thioguanine (4) afforded corresponding benzyl disulfide derivatives (5-8) in good yield. These compounds were converted easily to parent mercapto derivatives when they were treated with various reducing agents such as β-mercaptoethanol. Antitumor activity of compound 5 was higher than that of 1 both in ascites Sarcoma 180 and in Nakahara-Fukuoka sarcoma systems. However, toxicity and immunosuppressive activity of compound 5 and 6 were higher than those of 1 and 2, respectively.
著者
FUMIHIKO KANZAWA AKIO HOSHI KAZUO KURETANI
出版者
The Pharmaceutical Society of Japan
雑誌
Journal of Pharmacobio-Dynamics (ISSN:0386846X)
巻号頁・発行日
vol.3, no.8, pp.390-394, 1980 (Released:2008-02-19)
参考文献数
20
被引用文献数
1 1

5-Fluorouracil-resistant cell line designated as L5178Y/FU was established in this experiment. This is one of the colonies derived from the subculture which acquired resistance to 5-fluorouracil by passaging the L5178Y cells through ten successive episodes of culture in Fischer's medium containing 5-fluorouracil, in which each 5-fluorouracil treatment was followed by recovery intervals. The resistance of this line is about 80-fold that of the IC99 of 5-fluorouracil, and also shows a cross resistance to both 5-fluorouridine and 5-fluoro-2'-deoxyuridine. 5-Fluoro-2'-deoxyuridine resistant subline designated as L5178Y/FUdR was also isolated from the subculture which acquired resistance to 5-fluoro-2'-deoxyuridine by using the same selection procedure. The resistance of this line is about 650-fold that of the IC99 of 5-fluoro-2'-deoxyuridine, and shows a partial cross-resistance to 5-fluorouridine, but not to 5-fluorouracil.
著者
FUMIHIKO KANZAWA YUKA MATSUSHIMA JUNICHI ISHIHARA AKIO HOSHI TAKEO OHBA KENZO WATANABE
出版者
The Pharmaceutical Society of Japan
雑誌
Journal of Pharmacobio-Dynamics (ISSN:0386846X)
巻号頁・発行日
vol.9, no.8, pp.688-693, 1986 (Released:2008-02-19)
参考文献数
16
被引用文献数
5 5

A series of twenty six 5'-substituted FdUMP (5-fluoro-2'-deoxyuridine 5'-monophosphate) have been evaluated for their inhibitory effects on the proliferation of murine lymphoma L5178Y cells sensitive or resistant to FUdR (5-fluoro-2'-deoxyuridine). 5'-Octylphenylene-FdUMP was the most active among these active derivatives against the parent cell line (L5178Y/P). Several other FdUMP derivatives also proved as potent as FUdR in their antiproliferating activity on the L5178Y/P cell line. Activity of these derivatives was decresed considerably by a substituent with a long aliphatic chain and the introduction of acyl groups on the C-3' position. Eicosyl-FdUMP was found to show no or low cross-resistance on the L5178Y/FUdR subline which was about 19000-fold resistant to FUdR compared with the parent cell line. This derivative might penetrate cell membrane in an intact form and be converted into FdUMP by a phosphodiesterase inside the cell, because an anabolic enzyme, deoxyuridine kinase, was defective in cells of the L5178Y/FUdR subline. The derivatives were promising as antitumor agents for the treatment of relapsed patients following 5-fluorouracil therapy.
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 20

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.