文献一覧: 山脇一郎 (著者)

2 0 0 0 Studies on antitumor agents. IV. Syntheses and antitumor activities of compounds related to 1-(tetrahydro-2-furanyl)-5-fluorouracil metabolites.

著者: 上田修一武田節夫山脇一郎山下純一安本三治橋本貞夫
出版者: 公益社団法人日本薬学会
雑誌: CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
巻号頁・発行日: vol.30, no.1, pp.125-131, 1982
被引用文献数: 8

A hydroxylated metabolite of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT), 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (trans-3'-OH-FT, VIII) and its isomer, 1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (cis-3'-OH-FT, VI), were synthesized and isolated at high purity. As compounds related to FT metabolites, 2, 3'-anhydro-1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (2, 3'-anhydro-FT, V), 1-(2, 5-dihydro-2-furanyl)-5-fluorouracil (3', 4'-dehydro-FT, XII) and 1-(5-acetoxytetrahydro-2-furanyl)-5-fluorouracil (5'-AcO-FT, XI) were also synthesized. The antitumor activities of these compounds against sarcoma 180 and L 1210 were examined. The activities of cis-3'-OH-FT (VI) and 2, 3'-anhydro-FT (V) were found to be lower than that of FT. The activity of 5'-AcO-FT (XI) was the same as that of FT. 3', 4'-Dehydro-FT (XII) showed much greater activity than FT.

2014-10-19 06:38:49
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2 0 0 0 Studies on Antitumor Agents. V. Syntheses and Antitumor Activities of 5-Fluorouracil Derivatives

著者: 山下純一山脇一郎上田修一安本三治采見憲男橋本貞夫
出版者: 公益社団法人日本薬学会
雑誌: Chemical & pharmaceutical bulletin (ISSN:00092363)
巻号頁・発行日: vol.30, no.12, pp.4258-4267, 1982-12-25

Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2,4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1,3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2,4-di-O-substituted derivatives, 2,4-dibutoxy-5-fluoropyrimidine (1) and 2,4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180,respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

2014-10-19 06:38:34
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https://ci.nii.ac.jp/naid/110003634235

2 0 0 0 Piperazinealkanol Ester Derivatives of Indomethacin as Dual Inhibitors of 5-Lipoxygenase and Cyclooxygenase

著者: 山脇一郎鈴木雅博小川和男
出版者: 公益社団法人日本薬学会
雑誌: Chemical & pharmaceutical bulletin (ISSN:00092363)
巻号頁・発行日: vol.42, no.4, pp.963-971, 1994-04-15

Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B_2 (TXB_2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.

2014-10-12 08:10:04
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https://ci.nii.ac.jp/naid/110003631065

1 0 0 0 OA Studies on Antitumor Agents. V. Syntheses and Antitumor Activities of 5-Fluorouracil Derivatives

著者: 山下純一山脇一郎上田修一安本三治采見憲男橋本貞夫
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.30, no.12, pp.4258-4267, 1982-12-25 (Released:2008-03-31)
参考文献数: 32
被引用文献数: 15 18

Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2, 4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1, 3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2, 4-di-O-substituted derivatives, 2, 4-dibutoxy-5-fluoropyrimidine (1) and 2, 4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180, respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

2019-02-27 22:01:16
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1 0 0 0 OA Studies on Antitumor Agents. IV. Syntheses and Antitumor Activities of Compounds related to 1-(Tetrahydro-2-furanyl)-5-fluorouracil Metabolites

著者: 上田修一武田節夫山脇一郎山下純一安本三治橋本貞夫
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.30, no.1, pp.125-131, 1982-01-25 (Released:2008-03-31)
参考文献数: 20
被引用文献数: 5 8

2019-02-22 16:12:52
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1 0 0 0 OA Dimethyl(2-phenoxyethyl)sulfonium p-Toluenesulfonate の抗アレルギー剤開発におけるリード最適化

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: Chem-Bio Informatics Society
雑誌: Chem-Bio Informatics Journal (ISSN:13476297)
巻号頁・発行日: vol.3, no.4, pp.163-174, 2003 (Released:2003-12-31)
参考文献数: 10

I 型アレルギー疾患治療薬の開発を目的として dimethyl-2-phenoxyethylsulfoniun p-toluenesulfonate 誘導体(1)におけるリード最適化を行った。3-ethoxy, 3-phenoxy, 2,3-diethoxypropoxy 誘導体が、経口投与で誘導ラット同種受身皮膚アナフィラキシー(PCA)の抑制作用を示した。さらに急性毒性とアセチルコリン様作用を考慮し、2-[4-(3-ethoxy- 2-hydroxypropoxy)phenoxy]ethylsulfoniun p-toluenesulfonate (11)を前臨床試験候補化合物として選択した。

2018-09-25 23:49:53
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1 0 0 0 OA スルホニウム p -トルエンスルホン酸誘導体の抗アレルギー薬としての最適疎水性

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: Chem-Bio Informatics Society
雑誌: Chem-Bio Informatics Journal (ISSN:13476297)
巻号頁・発行日: vol.12, pp.25-38, 2012 (Released:2012-06-28)
参考文献数: 14
被引用文献数: 1

スルホニウム化合物の分配係数 logK 値は実測されていなかったので、これまでは置換基の πの計算値のみを用いてQSAR解析を報告してきた。本研究においては、固定相としてオクチルシリル化されたシリカゲルプレート(Merck HPTLC RP-8 F253S)、移動相として 50%(V/V) エタノール水溶液を用いて、抗アレルギー剤である Suplatast Tisilate (IPD-1151) の開発におけるスルホニウム化合物の logK 値を測定した。最適化された化合物 52 および 67 (Suplatast Tosilate)の logKTLC値は、それぞれ 0.07 と 0.06 であった。従って、抗アレルギー剤としてのスルホニウム化合物の望ましい logKTLC の値はほぼ 0 であることが判明した。

2018-09-25 12:49:04
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1 0 0 0 OA Suplatast Tosilate のリード化合物である Sulfonium p-toluenesulfonate 類の物理化学的性質と毒性の相関

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: 情報計算化学生物学会(CBI学会)
雑誌: Chem-Bio Informatics Journal (ISSN:13476297)
巻号頁・発行日: vol.1, no.2, pp.84-93, 2001 (Released:2001-09-28)
参考文献数: 12

スルホニウム化合物の物理化学的性質とその生物活性との相関を明らかにする目的で、スルホニウム化合物に特徴的な性質である H-D 交換およびメチル基転移反応速度を調べた。その結果H-D 交換およびメチル基の転移反応速度と急性毒性(LD50)の間に良好な相関があった。医薬品の開発において毒性をコントロールすることは非常に重要なことである。メチル基の高い反応性は急性毒性の面から望ましくない、従ってこれらスルホニウム化合物において、硫黄原子の置換基として不飽和炭素を持たない化合物が毒性軽減の面から望ましかった。さらに、OH 基もしくは COOH 基は大幅に毒性を軽減した。これらの毒性軽減に関する情報は抗アレルギー薬である Suplatast Tosilate の分子設計に用いられた。

2018-09-25 12:47:29
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1 0 0 0 OA Piperazinealkanol Ester Derivatives of Indomethacin as Dual Inhibitors of 5-Lipoxygenase and Cyclooxygenase

著者: 山脇一郎鈴木雅博小川和男
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.42, no.4, pp.963-971, 1994-04-15 (Released:2008-03-31)
参考文献数: 23
被引用文献数: 1 1

Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B2 (TXB2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.

2018-09-13 04:11:56
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1 0 0 0 OA 抗アレルギー剤の開発におけるLead Evolution; 第二リード化合物としてのDimethyl(2-Phenoxyethyl) sulfonium p-Toluenesulfonate

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: Chem-Bio Informatics Society
雑誌: Chem-Bio Informatics Journal (ISSN:13476297)
巻号頁・発行日: vol.2, no.3, pp.86-94, 2002 (Released:2002-10-31)
参考文献数: 10
被引用文献数: 1 1

I 型アレルギー疾患治療薬を開発する目的でトシル酸 2-ヒドロキシエチルジメチルスルホニウム (1) 誘導体の抗アレルギー作用を検討した。それらの中でトシル酸 2-アルコキシと2-フェノキシエチルジメチルスルホニウムの数化合物がIgE 誘導ラット同種受身皮膚アナフィラキシー(PCA)の抑制作用を示した。抗アレルギー作用および急性毒性と化合物の疎水性または電子的性質(HOMOまたは酸素原子上の電荷)との間に相関が見られた。そしてトシル酸2-フェノキシエチルジメチルスルホニウム(5)を、次の開発段階における第二のリード化合物として選定した。

2018-03-26 03:49:27
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1 0 0 0 抗アレルギー剤の開発におけるLead Evolution; 第二リード化合物としてのDimethyl(2-Phenoxyethyl) sulfonium p-Toluenesulfonate

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: 情報計算化学生物学会(CBI学会)
雑誌: CBIジャーナル (ISSN:13476297)
巻号頁・発行日: vol.2, pp.86-94, 2002
被引用文献数: 1

2017-04-22 20:48:25
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1 0 0 0 Suplatast Tosilate のリード化合物である Sulfonium p-toluenesulfonate 類の物理化学的性質と毒性の相関

著者: 多田幸雄山脇一郎上田修一松本宏松浦直資安本三治江田昭英堀幹夫
出版者: 情報計算化学生物学会(CBI学会)
雑誌: CBIジャーナル (ISSN:13476297)
巻号頁・発行日: vol.1, no.2, pp.84-93, 2001