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

SHOICHIRO OZAKI TOSHIO NAGASE HIROFUMI TAMAI HARUKI MORI AKIO HOSHI MASAAKI IIGO

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.9, pp.3894-3897, 1987-09-25 (Released:2009-10-19)

参考文献数

11

被引用文献数

8 9

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For the purpose of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, alkylthiomethyl, alkylsulfinylmethyl, alkylsulfonylmethyl, and acylthiomethyl groups were introduced at the 1- and 3-positions of 1. The antitumor activity of these synthetic compounds was tested against L1210 leukemia in mice. 1-Alkylthiomethyl-5-fluorouracils showed weak antitumor activity at a high dose (300 mg/kg).

著者

SUHAIL AHMAD SHOICHIRO OZAKI TOSHIO NAGASE MASAAKI IIGO REIKO TOKUZEN AKIO HOSHI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.10, pp.4137-4143, 1987-10-25 (Released:2009-10-19)

参考文献数

15

被引用文献数

23 24

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Antitumor-active derivatives of 5-fluorouracil were prepared via a new method by introducing an acyloxymethyl group at the 1-, 3-, or 1, 3-position (s). These derivatives were obtained by condensing 1, 3-bis (hydroxymethyl) -5-fluorouracil with various short-/long-chain carboxylic acids or their derivatives, in the presence of dicyclohexylcarbodiimide and a catalytic amount of N, N-dimethylaminopyridine. Some of the derivatives showed strong antitumor activity against the leukemia L1210 system when administered orally.

著者

Akio Hoshi Hiromi Watanabe Masatoshi Kobayashi Momoko Chiba Yutaka Inaba Naoto Kimura Takashi Ito

出版者

Tohoku University Medical Press

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.195, no.3, pp.163-169, 2001 (Released:2004-12-22)

参考文献数

31

被引用文献数

9 16

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Trace elements in sweat during sauna bathing were assessed. Sweat collected by the whole body method was compared with that collected by the arm bag method. The sweat samples were collected from ten healthy male adults aged 22-26 years, by heat exposure in dry sauna bathing (60°C, 30 minutes). Concentrations of major (Na, Cl, K, Ca, P and Mg) and trace (Zn, Cu, Fe, Ni, Cr and Mn) elements in sweat tended to be lower in the arm bag method than in the whole body method. It was found that Ca, Mg, Fe and Mn concentrations in the arm bag method were significantly lower than those in the whole body method. The amount of trace elements in sweat measured by the arm bag method was less than that by the whole body method; significant differences were observed in Fe and Mn amounts. These observations suggest that excretion of trace elements by sweating induces trace element decrease. Therefore, athletes and workers who work in a hot environment and sweat much habitually should ingest adequate amounts of trace elements.

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

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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

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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

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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.