著者

中尾 英雄 柳沢 宏明 杉村 征夫 平岡 哲夫

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.35, no.7, pp.563-574, 1977-07-01 (Released:2009-11-13)

参考文献数

36

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Synthetic studies on 7-methoxycephalosporins are reviewed under the following subjects : 1. synthesis of cephamycin derivatives 2. chemical methoxylation a) direct methods b) indirect methods 3. author's work a) synthesis by oxidation of novel Schiff bases b) synthesis from 7-haloacetamidocephalosporins 4. synthesis of new antibacterial derivatives.

著者

宮内 正雄 笹原 邦宏 藤本 光一 川本 勲 井手 純也 中尾 英雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.9, pp.2369-2374, 1989-09-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

10 9

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The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.

著者

宮内 正雄 笹原 邦宏 藤本 光一 川本 勲 井手 純也 中尾 英雄

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.37, no.9, pp.2369-2374, 1989

被引用文献数

9

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The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting &Delta;<SUP>3</SUP> cephalosporin ester proceeded mainly via isomerization to the &Delta;<SUP>2</SUP> ester and subsequent hydrolysis to the &Delta;<SUP>2</SUP> acid. Hydrolysis to the &Delta;<SUP>3</SUP> acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k<SUB>12</SUB> was approximately equal to the apparent degradation rate of the &Delta;<SUP>3</SUP> ester k<SUB>deg</SUB>, and slower than the hydrolysis rate of the &Delta;<SUP>2</SUP> ester k<SUB>24</SUB>. The isomerization process to the &Delta;<SUP>2</SUP> ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.

著者

宮内 正雄 栗原 英志 藤本 光一 川本 勲 井手 純也 中尾 英雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.9, pp.2375-2378, 1989-09-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

1 2

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The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of Δ3 cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the Δ2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the Δ2 ester (log k12) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the Δ3 ester (Δδ(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the Δ3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the Δ3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated π-bond system (C3=C4-C4=O) and consequently affects the feasibility of isomerization to the Δ2 ester, i.e., the stability to degradation.

著者

宮内 正雄 栗原 英志 藤本 光一 川本 勲 井手 純也 中尾 英雄

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.37, no.9, pp.2375-2378, 1989

被引用文献数

2

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The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of &Delta;<SUP>3</SUP> cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the &Delta;<SUP>2</SUP> ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the &Delta;<SUP>2</SUP> ester (log k<SUB>12</SUB>) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the &Delta;<SUP>3</SUP> ester (&Delta;&delta;(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the &Delta;<SUP>3</SUP> esters also correlated with log k<SUB>12</SUB>. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the &Delta;<SUP>3</SUP> ester (log k<SUB>21</SUB>) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated &pi;-bond system (C<SUB>3</SUB>=C<SUB>4</SUB>-C<SUB>4</SUB>=O) and consequently affects the feasibility of isomerization to the &Delta;<SUP>2</SUP> ester, i.e., the stability to degradation.

著者

中尾 英雄

出版者

三共総合研究所

雑誌

三共研究所年報 (ISSN:00806064)

巻号頁・発行日

no.27, pp.p1-41, 1975-12

著者

中尾 英雄

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.12, no.12, pp.983-986, 1976

著者

中尾 英雄 中山 英司

出版者

三共総合研究所

雑誌

三共研究所年報 (ISSN:00806064)

巻号頁・発行日

no.30, pp.p52-56, 1978-12

著者

中尾 英雄

出版者

三共総合研究所

雑誌

三共研究所年報 (ISSN:00806064)

巻号頁・発行日

no.31, pp.p134-137, 1979-12

著者

中尾 英雄 福島 正美 清水 総明 荒川 順生

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.94, no.8, pp.1032-1037, 1974-08-25 (Released:2008-05-30)

参考文献数

6

被引用文献数

12 14

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Water-soluble derivatives of N-(2-chloroethyl)-N-nitrosourea were synthesized and their antitumor activity was tested against leukemia L-1210. Most of these compounds showed a high activity.

著者

中尾 英雄 荒川 順生 中村 隆洋 福島 正美

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.9, pp.1968-1979, 1972-09-25 (Released:2008-03-31)

被引用文献数

24 31

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A series of 2, 5-bis (1-aziridinyl)-p-benzoquinone derivatives were synthesized and evaluated as antileukemic agents. The most active compounds against lymphoid leukemia L-1210 in BDF1 mice were 2, 5-bis (1-aziridinyl)-3-(2-carbamoyloxyethyl-1-methoxy)-6-methyl-p-benzoquinone, carbazilquinone (7), and related compounds (8, 23 and 24). Structure-activity relationships were discussed.

著者

中尾 英雄 荒川 順生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.20, no.9, pp.1962-1967, 1972-09-25 (Released:2008-03-31)

被引用文献数

8 13

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A series of p-benzoquinone derivatives having one or two carbamoyloxyalkyl groups in the 2 and/or 5-positions were synthesized and evaluated as antileukemic agents. Among these compounds 2, 5-bis (1-aziridinyl)-3-(2-carbamoyloxyethyl)-6-methyl-p-benzoquinone (21) showed high activity against lymphoid leukemia L-1210 in BDF1 mice.

著者

中尾 英雄 福島 正美 菅原 眞一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.93, no.11, pp.1526-1529, 1973-11-25 (Released:2008-05-30)

参考文献数

5

被引用文献数

2 2

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5-Cyano-2-furaldehyde and its derivatives were synthesized and their antimicrobial activities were tested. Neither series of compound possessed significant antimicrobial activity.