著者

丸本 龍二 吉岡 義夫 宮下 修 島 俊介 今井 欣一 川添 勝義 本庄 美喜男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.4, pp.759-774, 1975-04-25 (Released:2008-03-31)

被引用文献数

23 40

---

A large scale preparation of 2-haloadenosines (1) was attained by acetylation of 2-haloinosines (3), followed by chlorination and amination. 2-Alkoxyadenosines (5) were prepared in fairly good yields by protection of both 2'- and 3'-hydroxyl groups of 2-chloroadenosine (1a) or 2-chloroinosine (3a), followed by substitution of the chlorine atom with alkoxy group. In the reaction of 1a with sodium alkoxide, there were obtained some oligomers of 5, of which the structures were elucidated. The reaction of 5-amino-4-cyano-1-β-D-ribofuranosylimidazole with carbon disulfide afforded 2, 6-di-mercapto-9-β-D-ribofuranosylpurine (15), which was converted to 2-mercaptoadenosine (14e) and its S-substituted derivatives. 2-Phenylaminoadenosine (29e) was prepared with comparative ease via 2-phenylamino-2', 3', 5'-tri-O-acetylinosine (32), the synthesis of which was effected by acetylation of 2-phenylaminoinosine (30) with acetylchloride in acetic acid. Many 2-substituted adenosines including O-substituted 2-hydroxyadenosines, S-substituted 2-mercaptoadenosines, N2-substituted 2-aminoadenosines, 2-alkyl- and -aryl-adenosines were prepared, among which several compounds were found to have a remarkable coronary vasodilating potency. Compound (29e) showed not only a strong potency, but also a longer duration of the effect than that of 1a. The structure-coronary vasodilating activity relationship was also discussed.

著者

丸本 龍二 本庄 美喜男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.22, no.1, pp.128-134, 1974-01-25 (Released:2008-03-31)

被引用文献数

31 41

---

The reaction of uridine with acyl bromide in acetonitrile (or ethyl acetate) afforded 3', 5'-di-O-acyl-2'-bromo-2'-deoxyuridine (II, V) in good yield, which was converted to 2'-deoxyuridine by hydrogenation and subsequent deacylation. A silmiar reaction of N4-acetylcytidine with acetyl bromide yielded 1-(2, 5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)-N4-acetylcytosine (VIII), which was converted to 3'-deoxycytidine (X) by hydrogenation and subsequent deacylation with a concomitant formation of 2', 3'-dideoxycytidine (XII) and to 1-β-D-arabinofuranosyl cytosine (XI) by treatment with potassium hydroxide in ethanol. A similar reaction of cytidine with acyl bromide gave 2, 2'-anhydro-1-(3, 5-di-O-acyl-β-D-arabinofuranosyl) cytosine hydrobromide (XIV, XVI). These reaction mechanisms were also presented.

著者

上田 武雄 辻 忠和 百名 弘子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.11, no.7, pp.912-917, 1963-07-25 (Released:2008-03-31)

被引用文献数

3 7

---

The replacement of 4-hydroxyl group of aminopyrimidinols by sulfhydryl in one step, through the action of phosphorus pentasulfide in triethylamine or 3-picoline. 5-Acylamino-6-amino-4-pyrimidinols were treated with phosphorus pentasulfide in pyridine, to yield thiazolo [5, 4-d] pyrimidine and 6-purinethiol compounds. The yield of both two type compounds were changed according to a functional group in the starting substance. These products, in addition, other 6-purinethiol and related compounds were screened as to their antiviral activities on poliomyelitis virus. Any of the compounds, however, did not exert a significant activity on the virus.

著者

桜井 邦好 青柳 栄 豊福 初則 大木 実 吉沢 豊吉 黒田 敏男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.11, pp.3565-3566, 1978-11-25 (Released:2008-03-31)

被引用文献数

3 4

---

Selective N1-tetrahydrofurylation of uracils has been performed in satisfactory yield by direct addition of uracils to 2, 3-dihydrofuran in the presence of PCl5 in hexamethyl-phosphoramide (HMPA).

著者

野村 容朗 吉岡 義夫 南 功

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.27, no.4, pp.899-906, 1979-04-25 (Released:2008-03-31)

被引用文献数

7 13

---

Addition of 5-fluorouracil (1) to the double bond of 2, 3-dihydrofuran (3) without using any catalyst progressed smoothly at an elevated temperature and afforded an equilibrium mixture of 1-(tetrahydro-2-furyl)-5-fluorouracil (5) and 1, 3-bis (tetrahydro-2-furyl)-5-fluorouracil (7). By choosing favourable reaction conditions, each of these compounds was obtained in high yield. Thermal decomposition of 7 gave an equimolar mixture of 3 and 5. At a higher temperature, 5 underwent thermal reaction to yield 1 and 3. Study of the present addition reaction was extended to other 5-substituted uracils (8, R=-H, -CH3, -Cl, -Br, -COOCH3, -CONH2, -CN) which furnished the corresponding 1-(tetrahydro-2-furyl)-and 1, 3-bis (tetrahydro-2-furyl)-derivatives (9-15, 18-23) with high yields. A very small amount of 3-(tetrahydro-2-furyl)-5-substituted uracils (6, 16, 17) by-produced in the reactions was isolated and the structures unequivocally identified.

著者

丸中 照義 南 慶典 梅野 幸彦 安田 昭男 佐藤 俊幸 藤井 節郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.6, pp.1795-1803, 1980-06-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

7 6

---

Four metabolites of the antitumor agent 1-(tetrahydro-2-furanyl)-5-fluorouracil, formed in vitro by rat liver microsomes, were isolated by thin-layer chromatography or high-performance liquid chromatography. On the basis of mass spectrometry, 1H-NMR spectral analysis, and comparison with authentic samples, these metabolites were identified as 1-(trans-4-hydroxytetrahydro-2-furanyl)-5-fluorouracil, 1-(cis-4-hydroxytetrahydro-2-furanyl)-5-fluorouracil, 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil and 1-(4, 5-dehydrotetrahydro-2-furanyl)-5-fluorouracil. These metabolites were also found in the plasma and urine of rats after administration of 1-(tetrahydro-2-furanyl)-5-fluorouracil.

著者

鴻巣 俊之 田島 和 武田 憲子 宮岡 武男 笠原 真由美 安田 紘 老田 貞男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.10, pp.2581-2589, 1991-10-25 (Released:2008-03-31)

参考文献数

7

被引用文献数

9 16

---

New triazole compounds were designed and synthesized as potential inhibitors of the fungal cytochrome P-450 14α-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (2R, 3R)-3-acylamino-2-aroyl-2-butanol derivatives III exhibited remarkably high efficacy after oral or parenteral administration. The structure-activity relationships of these amidoalcohols were evaluated.

著者

相山 律男 永井 久子 沢田 誠吾 横倉 輝男 糸川 秀治 中西 守

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.10, pp.2810-2813, 1992-10-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

12 16

---

Self-association of irinotecan hydrochloride (CTP-11) in an aqueous solution was studied using UV, circular dichroism (CD), 1H-NMR and the quasi-elastic light scattering (QLS) method. The UV spectra showed a hypochromic effect in the aqueous solution. In the CD spectra, typically positive Davydov splitting was observed and the Δε value was reduced sigmoidally when the concentraion of CTP-11 was decreased. In the 1H-NMR, the aromatic signals of higher concentration shifted to a diamagnetic direction compared with those of lower concentration. These observations suggested that CPT-11 molecules are present as monomer in the lower concentration, and the self-association with positive helicity occurs by vertical stacking more than 10 μM of concentration. Its molecules form complete aggregates at more than 2 mM of the concentration. Results of QLS which coincided in the prediction of partition coefficient experiments suggested that CPT-11 molecules formed dimer under the condition. By the regression analysis of CD spectral data, the equilibrium constant for the self-association was calculated to be 2.41×10-4 M-1.

著者

山田 幸子 石川 正幸 金子 主税

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.11, pp.2818-2834, 1975-11-25 (Released:2008-03-31)

被引用文献数

12 22

---

Photolysis of a series of acridine 10-oxides (Ia-Ig) in various solvents is reported. The structures of photo-products were determined by syntheses, chemical transformation to the known compounds, or by direct examination of their spectroscopic data. Based on the structures of photo-products and the solvent effect on the product distribution in these photolyses, a mechanistic rationalization of these photo-reactions is presented. The characteristic features of the photo-rearrangement reactions of acridine 10-oxides are discussed and compared with those of bicyclic and monocyclic azine N-oxides, e, g., quinoline 1-oxides and pyridine 1-oxides.

著者

沢田 誠吾 宮坂 貞 荒川 基一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.1, pp.275-287, 1978-01-25 (Released:2008-03-31)

被引用文献数

2 2

---

1-(Substituted-phenyl)-2, 3-tetramethylenepyrrolo [2, 1-b] benzothiazoles (IV-2-IV-17) were synthesized from the correspoding 3-(substituted-phenyl) thiazolo [2, 3-b] benzothiazolium perchlorates (III) by the reaction of 1-morpholino-1-cyclohexene, an enamine. On reaction with cuprous cyanide p-substituted bromobenzene (IV-2) furnished benzonitrile (IV-23), which was converted into the corresponding 1-phenyl derivatives (IV) with various aliphatic functional groups at the para position of the phenyl moiety. On reaction with methylmagnesium iodide and subsequent acid hydrolysis IV-23 was converted into acetophenone (IV-24), which reacted with methyltriphenylphosphylene to give 2-phenylpropylene (IV-38). Hydroboration of IV-38 afforded 2-phenylpropanol (IV-39), which was oxidized into the corresponding propionic acid (IV-43), the sulfur atom being oxidized at the same time into sulfoxide. Deoxygenation of the ester (IV-44) was successfully carried out with PBr3 to obtain the desired α-phenyl substituted propionic acid ester (IV-45).

著者

沢田 誠吾 宮坂 貞 荒川 基一

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.25, no.12, pp.3370-3375, 1977-12-25 (Released:2008-03-31)

被引用文献数

5 5

---

Seventeen 3-(substituted-phenyl) thiazolo [2, 3-b] benzothiazolium perchlorates (3) were synthesized by acid-cyclization of the ketosulfides (2), which were prepared by alkylation of 2-mercaptobenzothiazole sodium salt with substituted phenacyl halides (1). Some of the phenacyl halides were prepared by chloroacetylation of substituted benzenes, and the others by bromination of the corresponding substituted acetophenones.

著者

沢田 誠吾 八重樫 隆 古田 富雄 横倉 輝男 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.2, pp.310-313, 1993-02-15 (Released:2008-03-31)

参考文献数

22

被引用文献数

13 20

---

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

八重樫 隆 沢田 誠吾 古田 富雄 横倉 輝男 山口 健太郎 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.5, pp.971-974, 1993-05-15 (Released:2008-03-31)

参考文献数

10

被引用文献数

6 10

---

The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-etylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c-e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.

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

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.1, pp.131-135, 1992-01-25 (Released:2008-03-31)

参考文献数

19

被引用文献数

9 10

---

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 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

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.12, pp.3183-3188, 1991-12-25 (Released:2008-03-31)

参考文献数

28

被引用文献数

39 57

---

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

HIROYUKI HAYAKAWA KAZUHIRO HARAGUCHI HIROMICHI TANAKA TADASHI MIYASAKA

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.1, pp.72-79, 1987-01-25 (Released:2009-10-19)

参考文献数

16

被引用文献数

29 43

---

The sugar moiety of adenosine, inosine, or guanosine was protected with a tert-butyldimethylsilyl group. The C-8 lithiation of these protected nucleosides was carried out with lithium diisopropylamide in tetrahydrofuran at below -70°C. The reactions of the C-8-lithiated species with MeI, HCO2Me, and ClCO2Me were examined. The resulting products having a carbon substituent at the C-8 position were converted to the corresponding 8-carbon-substituted purine nucleosides by treatment with tetrabutylammonium fluoride. The whole sequence constitutes a simple method for the preparation of 8-carbon-substituted purine nucleosides from intact purine nucleosides.

著者

山根 晃 井上 英夫 上田 亨

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.1, pp.157-162, 1980-01-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

10 19

---

Treatment of 4-thiouridine with phenacyl bromide, bromoacetone, and ethyl bromoacetate gave the corresponding 4-thioalkylcarbonyl derivatives. The sulfur extrusion reactions of these compounds afforded ribosides of 4-phenacylidene-2 (3H)-pyrimidinone, 4-acetonylidene-2 (3H)-pyrimidinone, and 2-pyrimidinone-4-acetic ester, respectively. The ease of sulfur extrusion depends on the electron-withdrawing ability of the carbonyl group attached to the 4-S-methylene group. Sulfur extrusion reactions starting from 6-thioinosine similarly gave the ribofuranosides of 6-phenacylpurine and 6-acetonylpurine. These purine ribosides exist meinly as the enol form rather than the keto form.

著者

山根 晃 松田 彰 上田 亨

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.1, pp.150-156, 1980-01-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

13 26

---

Treatment of 6-methylsulfonyl-9-(2, 3, 5-tri-O-benzoyl-β-D-ribofuranosyl) purine with ethyl acetoacetate and sodium hydride in tetrahydrofuran afforded, after deblocking, 6-ethoxycarbonylmethyl-9-β-D-ribofuranosylpurine. Similarly, replacement of the 6-methylsulfonyl moiety with other carbanions derived from diethyl malonate, ethyl cyanoacetate, malononitrile, nitromethane, and sodium cyanide gave the corresponding 6-C-substituted purine nucleosides. Most of these derivatives exist as the 6-(1H)-exomethylene tautomeric forms. 6-Ethoxycarbonylmethylpurine riboside was further converted to 6-methyl, ethyl, propyl, butyl, and pentyl-purine ribosides by decarboxylation or prior alkylation of the methylene group followed by de-carboxylation. This reaction sequence facilitated the preparation of hitherto almost inaccessible alkyl or C-substituted purine nucleosides.

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

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.6, pp.1446-1454, 1991-06-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

144 197

---

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 野方 健一郎 古田 富雄 横倉 輝男 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.10, pp.2574-2580, 1991-10-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

44 56

---

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.