著者

安原 陽平

出版者

早稲田大学大学院社会科学研究科

雑誌

社学研論集 (ISSN:13480790)

巻号頁・発行日

no.17, pp.161-176, 2011

著者

内野 善生 佐々木 成人 中陦 克己 板東 武彦 本郷 利憲 森 茂美 森 大志

出版者

日本生理学会

雑誌

日本生理学雜誌 (ISSN:00319341)

巻号頁・発行日

vol.63, no.10, pp.271-316, 2001-10-01

被引用文献数

2

著者

シイジュン ティエン ユージン イマダ イボシ パール

出版者

環太平洋産業連関分析学会

雑誌

産業連関 (ISSN:13419803)

巻号頁・発行日

vol.17, no.1, pp.30-41, 2009

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本稿では,ツーリズム・サテライト・アカウント(TSA)の手法によりハワイの観光産業の規模を検証する.調査結果から,ハワイでは 2007 年の州内総生産(GDP)の 14.7%,雇用全体の 15%,所得全体の 12.6%,州の税収の 20.1%を直接的に観光産業が占めていることが明らかになった.観光による間接的な影響も含めれば,2007 年では観光がハワイの雇用全体の 19.6%,州の税収の 24.5%を占めている.ハワイの観光部門は最多の雇用を生み出している部門であるにもかかわらず,収益を生み出すことには 3 位の部門に甘んじている.

著者

安藤俊夫

雑誌

癌と化学療法

巻号頁・発行日

vol.15, pp.1-14, 1998

被引用文献数

1

著者

沢田 誠吾 野方 健一郎 古田 富雄 横倉 輝男 宮坂 貞

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.39, no.10, pp.2574-2580, 1991-10-25

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A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl-(4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

著者

八重樫 隆 野方 健一郎 沢田 誠吾 古田 富雄 横倉 輝男 宮坂 貞

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.40, no.1, pp.131-135, 1992-01-25

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Water-soluble derivatives having the lactone ring intact were synthesized starting from 7-ethyl-10-hydroxycamptothecin (1). Glycosides (2) of the phenolic hydroxyl group of 1 were obtained by reaction with acetylated α-bromosugars in acetone or aqueous acetone in the presence of potassium carbonate, followed by deprotection.Phosphates (3) were prepared by reaction of 1 with phosphoryl chloride in pyridine or with dibenzylchlorophosphoridate.Sulfates (4) were obtained by reaction of 1 with sulfur trioxide-pyridine complex in the presence of a tertiary amine.The organic ammonium salts of monophosphate (3p) and sulfates (4a and 4b) showed significant activity against L1210 in vivo.

著者

沢田 誠吾 八重樫 隆 古田 富雄 横倉 輝男 宮坂 貞

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.41, no.2, pp.310-313, 1993-02-15

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7-Ethylcamptothecin (1d), a model which does not have any site on the A-ring for further modification was converted into water-soluble derivatives by opening the E-ring lactone. 1d was heated in N, N-dimethylenediamine to yield amide 2a, and this was then acylated to furnish 3a-q, which were soluble in water as their HCl salts. The propionyl (3b), butyryl (3c) and methylthiopropionyl (3h) derivatives showed higher activity than the sodium salt of 1d. The acyl group makes the derivatives more lipophilic, and ease of hydrolysis of amide 2a to 1d is thought to be necessary for significant activity.

著者

Matsuda Akira Takenuki Kenji Itoh Hiroko Sasaki Takuma Ueda Tohru

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.35, no.9, pp.3967-3970, 1987

被引用文献数

32

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We have synthesized 2'-deoxy-2' (S) -methylcytidine (7), a new antileukemic nucleoside. The carbonyl methylation of 2'-ketonucleoside (1) with MeLi, Me<SUB>3</SUB>Al and MeMgX was examined. Only in the reaction with MeMgX, did the more hindered &beta;-attack afford the 2'-methyl-t-alcohol (2b). Compound 2b was converted into the methyl oxalate (4), which was subjected to radical deoxygenation to give the 2'-deoxy-2' (S) -methyl derivative (5). The deprotection of 5 followed by substitution with NH<SUB>3</SUB> furnished 7. The structure-activity relationships of 7 and some other 2'-branched-chain sugar cytidines against L1210 cells are also described.

著者

松田 彰 南川 典昭 佐々木 琢磨 上田 亨

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.36, no.7, pp.2730-2733, 1988

被引用文献数

32

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The design, synthesis and antileukemic activity of 5-alkynel-1-&beta;-D-ribofuranosylimidazole-4-carboxamides (6) are described. The cross-coupling reaction of 5-iodo-1-(2, 3, 5-tri-O-acetyl-&beta;-D-ribofuranosyl)imidazole-4-carboxamide (8) with various terminal alkynes in the persence of bis(benzonitrile)palladium dichloride and triethylamine in acetonitrile gave 5-alkylnyl derivatives (9) in high yields. Coupling of 8 with (trimethylsilyl)acetylene gave hte undesired dimer (10). Instead of (trimethylsilyl)acetylene, treatment of trimethyl[(tributyl-satannyl)ethynyl]silane with 8 in the absence of triethylamine produced the desired 5-[2-(trimethylsilyl)ethynyl] derivative (9f) in 77% yield. Deblocking of these nucleosides (9) gave the target nucleosides (6a-f). Among them, 5-ethynyl-1-&beta;-D-ribofuranosylimidazole-4-carboxyamide (6f) is the most potent inhibitor of the growth of murine L1210 cells in vitro (IC<SUB>50</SUB>=0.18 &mu;g/ml).

著者

松田 彰 伊藤 弘子 竹貫 健二 佐々木 琢磨 上田 亨

出版者

公益社団法人日本薬学会

雑誌

Chem. Pharm. Bull. (ISSN:00092363)

巻号頁・発行日

vol.36, pp.945-953, 1988

被引用文献数

1

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The reaction of 4-ethoxy-1-(3,5-O-tetraisopropyldisiloxanyl-1,3-diyl-β-D-erythro-pentofuran-2-ulosyl)-2(1H)-pyrimidinone (11) with various organometallic reagents yielded corresponding 2'-branched-chain sugar pyrimidine nucleosides. Only in the reactions with MeMgBr and EtMgBr was the more hindered β-attack observed to afford and 2'-alkyl ribofuranosides (13a, b). In the reaction of 11 with MeLi, Me_3,Al, or PhMgBr, 2'-methyl or phenyl arabinosides (12a, b, c)were obtained stereoselectively. Conversion of these pyrimidine nucleosides into cytosine derivatives is also described and their antileukemic and antiviral activities are discussed.

著者

松田 彰 南川 典昭 佐々木 琢磨 上田 亨

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.36, no.7, pp.2730-2733, 1988-07-25

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The design, synthesis and antileukemic activity of 5-alkynel-1-β-D-ribofuranosylimidazole-4-carboxamides (6) are described. The cross-coupling reaction of 5-iodo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide (8) with various terminal alkynes in the persence of bis(benzonitrile)palladium dichloride and triethylamine in acetonitrile gave 5-alkylnyl derivatives (9) in high yields. Coupling of 8 with (trimethylsilyl)acetylene gave hte undesired dimer (10). Instead of (trimethylsilyl)acetylene, treatment of trimethyl[(tributyl-satannyl)ethynyl]silane with 8 in the absence of triethylamine produced the desired 5-[2-(trimethylsilyl)ethynyl] derivative (9f) in 77% yield. Deblocking of these nucleosides (9) gave the target nucleosides (6a-f). Among them, 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxyamide (6f) is the most potent inhibitor of the growth of murine L1210 cells in vitro (IC_<50>=0.18 μg/ml).

著者

江島 明男 寺沢 弘文 杉森 正道 大薄 悟 松本 建介 川戸 康義 安岡 周美 田川 博昭

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.40, no.3, pp.683-688, 1992

被引用文献数

21

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Several E-ring-modified analogues of (RS)-camptothecin were synthesized by total synthesis via Friedlander condensation and evaluated for cytotoxicity and antitumor activity against P388 mouse leukemia cells. Among them, (RS)-20-deoxyamino-7-ethyl-10-methoxycamptothecin (25c) was found to be more active than (RS)-camptothecin (1) in the in vivo assay.

著者

渋井 壮一郎

出版者

日本脳神経外科学会

雑誌

Neurologia medico-chirurgica (ISSN:04708105)

巻号頁・発行日

vol.24, no.2, pp.65-72, 1984

被引用文献数

1

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The antitumor effect of 5'-deoxy-5-fluorouridine (5'-DFUR) against experimental glioma cells was investigated in vitro and in vivo. 5'-DFUR is a newly synthesized masked compound of 5-FU, which is activated only in the presence of pyrimidine nucleoside phosphorylase. This enzyme has been reported to exist much more in malignant tumors, such as Sarcoma 180 and Ehrlich ascites carcinoma, than in normal tissues. The activities analysed in 9L, RG12, and 203GL cells were 24.3, 75.1, and 8.1% respectively of the activity in Sarcoma 180. Normal rat brain showed 22.8% of the activity. Growth curves of cultured 9L and RG12 cells showed a dose-dependent 5'-DFUR antitumor effect when it was used at a concentration of over 10 &mu;gml. The colony forming rate of 9L cells treated with 20 &mu;gml of 5'-DFUR decreased to 10%. The inhibition rate of 203GL cells transplanted subcutaneously into C57BL mice was 52.3% in weight, and that of human glioblastoma cells transplanted subcutaneously into nude mice was 20.9% in size after treatment with 5'-DFUR, 400 mgkgday for ten consecutive days. When 9L cells were transplanted intracranially into CD Fisher rats, their median survival time became four days longer than that of non-treated rats. Flowcytometric analysis of in vitro 9L cells and in vivo 203GL cells showed an accumulation in the cells between the 2C and 4C components after treatment of 5'-DFUR. It seems that a delay in DNA synthesis occurred in the presence of this drug. This newly synthesized antitumor drug is expected to be effective for the treatment of malignant brain tumors.

著者

寺沢 弘文 江島 明男 杉森 正道

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.49, no.11, pp.1013-1020, 1991

被引用文献数

4

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現在臨床評価が進んでいるCPT-11あるいはTopotecanは, いずれも植物から抽出した天然のCPTを原料とした半合成で製造されているが, 植物中の含有量が少ないことから大量供給には問題が残されており, また, 植物の成長が天候に大きく左右されることを考えると, 安定供給という面からも効率の良いCPTの合成法が望まれている。今回我々は, 天然型CPTの合成法の検討を行い, 光学分割および不斉合成法により, 天然型CPT合成のkeyとなる光学活性な3環性化合物の合成に成功し, 天然型CPTの大量合成に対応可能な効率的合成法を開発した。さらに, この3環性化合物を活用し, CPTの構造活性相関を探るべく骨格あるいは置換基の変換を検討した結果, <I>in vivo</I>および<I>in vivo</I>において非常に強い抗腫瘍効果を持つ, 新規な骨格の6環性化合物を得ることができた。CPTの単離, 構造決定から4半世紀が経過した現在, 再びCPTが脚光を浴びているのは, CPT-11が臨床試験で優れた効果を示し, 高い評価を受けていること, およびCPTのトポイソメラーゼIの阻害という全く新しい作用メカニズムが明らかにされたという2つの理由に拠る所が大きい。CPT-11, Topotecanに次いで9-アミノーCPTあるいは10, 11-メチレンジオキシーCPTなどが前臨床研究の段階にあり, しばらくはCPTに関する話題が尽きないであろう。

著者

沢田 誠吾 野方 健一郎 古田 富雄 横倉 輝男 宮坂 貞

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.39, no.10, pp.2574-2580, 1991

被引用文献数

56

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A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl-(4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

著者

沢田 誠吾 松岡 俊一 野方 健一郎 永田 洋 古田 富雄 横倉 輝男 宮坂 貞

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.39, no.12, pp.3183-3188, 1991

被引用文献数

57

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20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity o the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.

著者

沢田 誠吾 岡島 悟 相山 律男 野方 健一郎 古田 富雄 横倉 輝雄 杉野 栄一 山口 健太郎 宮坂 貞

出版者

公益社団法人日本薬学会

雑誌

Chem. Pharm. Bull. (ISSN:00092363)

巻号頁・発行日

vol.39, pp.1446-1454, 1991

被引用文献数

9

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Nevel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HC1 salts wiht the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors.The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.

著者

沢田 誠吾 岡島 悟 相山 律男 野方 健一郎 古田 富夫 横倉 輝男 杉野 栄一 山口 健太郎 宮坂 貞

出版者

福山大学

雑誌

福山大学薬学部研究年報 (ISSN:0288724X)

巻号頁・発行日

vol.10, pp.67-68, 1992

著者

八重樫 隆 沢田 誠吾 永田 洋 古田 富雄 横倉 輝男 宮坂 貞

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.12, pp.2518-2525, 1994

被引用文献数

42

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Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedlander's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH<SUB>2</SUB>CH<SUB>2</SUB>SCH<SUB>3</SUB>) and 8f (11-F, O-COC<SUB>2</SUB>H<SUB>5</SUB>) showed activity towards Meth A in mice that was comparable to that of CPT-11, at lower doses than CPT-11.

著者

八重樫 隆 沢田 誠吾 永田 洋 古田 富雄 横倉 輝男 宮坂 貞

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.12, pp.2518-2525, 1994-12-15

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Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedlander's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH_2CH_2SCH_3) and 8f (11-F, O-COC_2H_5) showed activity towards Meth A in mice that was comparable to that of CPT-11,at lower doses than CPT-11.