著者

松永 康志 大田 涼子 坂東 信行 山田 博章 湯浅 宏 金谷 芳雄

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.4, pp.720-724, 1993-04-15 (Released:2008-03-31)

参考文献数

10

被引用文献数

6 13

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(E)-4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-(4-isopropyl)phenyl]-1-butenyl]phenyl monophosphate (TAT-59) is a new drug for the treatment of breast cancer. Physical and chemical stability of a tablet consisting of TAT-59 powder and a few excipients (Formulated tablet), a tablet consisting of only TAT-59 power (TAT-59 tablet) and TAT-59 powder itself itself was evaluated based on water content, tensile strenght, porosity, the amount of TAT-59 and its hydrolysis product, DP-TAT-59.The water content of Formulated tablet increased with relative humidity (RH), whereas that of TAT-59 tablet and TAT-59 powder scarcely changed. The equilibrium water content of Formulated tablet was much greater than that of the TAT-59 tablet or TAT-59 powder due to adsorbed moisture by the excipients. The tensile strength and porosity of Formulated tablet decreased and increased linearly, respectively, with increasing water content. The degradation rate of TAT-59 decreased in the following order : Formulated tablet>TAT-59 tablet>TAT-59 powder. The relationship between equilibrium water content and degradation rate of the Formulated tablet was determined by the Carstensen equation, in which the interaction order between the durg and water content was 1.9, and the degration of TAT-59 in Formulated tablet was related to water content. Thus, it was found that the degradation of TAT-59 was accelerated by compression and addition of excipients.

著者

Takahiro Uchida Yuka Sugino Mai Hazekawa Miyako Yoshida Tamami Haraguchi

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.60, no.8, pp.949-954, 2012-08-01 (Released:2012-08-01)

参考文献数

13

被引用文献数

4 6

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The bitterness of 10 different products with ambroxol as active ingredient, the original and nine generics, were evaluated by human gustatory sensation tests in which the tablets were kept in the mouth, with water, at 20 and 37°C. The products all showed different bitterness intensities. The original and some of the generic products had comparatively low bitterness intensities but some of the generic products had comparatively high bitterness intensities. The bitterness intensities of these 10 was found to be significantly correlated with both the disintegration time, as evaluated using the ODT-101 (a recently developed apparatus), and the drug concentration in dissolved medium, as measured in a conventional dissolution test. The bitterness threshold of ambroxol solution was found to increase when the temperature of the water with which the tablets were taken, was raised from 20 to 37°C. The equation was calculated to predict the bitterness intensity of ambroxol, a function based on temperature and the ambroxol concentration using data from a standard ambroxol solution at 4, 20 and 37°C. The bitterness intensities obtained for the 10 ambroxol formulations with water at 20 and 37°C, coincided with the bitterness values predicted by the equation.

著者

瀬沼 勝 柴崎 昌隆 西本 茂 柴田 恵次郎 岡村 公生 伊達 忠正

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.37, pp.3204-3208, 1989

被引用文献数

1

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Practical resolution of (2RS, 3RS)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionic acid (2) was examined by the use of several basic amino acids. L-Lysine was found to be the most effective resolving agent to obtain (+)-(2S, 3S)-2,a key intermediate for the synthesis of diltiazem (1). This new method should be applicable to the industrial production of 1 in view of the simplicity of the procedure, the ready availability of L-lysine, and the high yield of the desired isomer. The absolute stereochemistry of (+)-2 was determined to be 2S, 3S by X-ray crystallographic analysis.

著者

瀬沼 勝 藤井 武彦 瀬戸 正彦 岡村 公生 伊達 忠正 絹巻 明生

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.38, no.4, pp.882-887, 1990-04-25

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The direct resolution of (3aRS, 6SR, 6aSR)-1,3-dibenzyl-6-hydroxy-3,3a, 6,6a-tetrahydro-1H-furo[3,4-d]imidazole-2,4-dione [(±)-9], a key intermediate for biotin, with optically active amines was examined. Reaction of (±)-9 with cinchonidine readili gave the cinchonidine salt of the (4S, 5R)-aldehyde-carboxylic acid (12), acidification of which gave (3aS.6R, 6aR)-9,convertible to biothin. N-alkyl-D-glucamines (14) were also found to be effective resolving agents for (±)-9 applicable for industrial use. Reutilizatin of the unwanted epimer [(3aR, 6S, 6aS)-9] was effected by facile oxidation to the meso-diacid (3) with sodium chlorite.

著者

吉岡 龍藏 大槻 理 瀬沼 勝 土佐 哲也

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.4, pp.883-886, 1989-04-25

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A practical preparation of D-aspartic acid β-methyl ester [D-Asp(OMe)], a raw material for the antibiotic aspoxicillin, has been developed by the use of a second-order asymmetric transformation. The diastereomeric resolution of DL-Asp(OMe) with (-)-1-phenylethanesulfonic acid (PES) resulted in salt formation of less soluble D-・(-) and more soluble L-・(-) in acetonitrile. The soluble L-・(-) was easily epimerized into DL-・(-) by heating it in acetonitrile in the presence of catalysts. Attempted fractional crystallization of DL-・(-) or L-・(-) under such epimerizing conditions led to the desired D-・(-) in 90% yield via equilibrium asymmetric transformation in a solid-liquid heterogeneous system. Details of optimum techniques for the asymmetric transformation are presented.From these results, unique preparation processes of both D-Asp(OMe) and D-p-hydroxyphenylglycine, important intermediate materials for aspoxicillin, have been achieved by asymmetric transformation using chiral PES as the resolving agent.

著者

三橋 博 金子 光 佐々木 希吉

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.10, no.11, pp.1119-1122, 1962-11-25

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It was shown that DL-phenylalanine [2-^<14>C] was incorporated into C-3 of two kinds of isoflavone, formononetin and genistein, by Trifolium pratense sp., in vivo. These results indicate that the aryl group undergoes a migration within the C_6-C-C-C fragment, and this observation agrees with Grisebach's experimental data.

著者

伊東 秀之 三宅 陽子 吉田 隆志

出版者

公益社団法人 日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.7, pp.1260-1262, 1995

被引用文献数

32

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Three new piscicidal triterpenens named irisgermanicals A, B and C along with seven known iridal-type triterpenes including iripallidal and iriflorental were isolated from the bark of Iris germanica rhizome, upon bioassay-guided fractionation using the Medaka (killie-fish; Oryzias latipes), and their bicyclic structures were elucidated based on the spectral analyses. Irisgermanicals B and C were characterized as geometrical iriflorental and iripallidal isomers, respectively, concerning the α, β-unsaturated aldehyde moiety. The piscicidal activity was observed for bicyclic iridals, among which iriflorental exhibited most potent activity.

著者

松田 彰 小尾 紀行 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.33, no.6, pp.2575-2578, 1985-06-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

13 18

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Reaction of 2', 3', 5'-tri-O-benzoyluridine (3) with 1-methylimidazole in the presence of phosphoryl chloride in acetonitrile afforded 3-methyl-1-imidazolium intermediate (4), from which a variety of 4-substituted pyrimidin-2 (1H)-one ribosides (5-12) were obtained in a one-pot manner by nucleophilic substitutions under mild conditions. Application of this method to 2'-deoxyriboside of several pyrimidines (13a, b, c) is also described.

著者

宮下 修 松村 興一 笠原 俊彦 島津 浩 橋本 直人

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.3, pp.887-898, 1982-03-25 (Released:2008-03-31)

参考文献数

6

被引用文献数

3 8

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Various derivatives of 5-fluoro-5, 6-dihydrouracil with an alkoxycarbonyl, substituted carbamoyl, or cyano group at C-5, and one of a variety of substituents, i.e., alkoxy, substituted mercapto, substituted amino, acyl amino, and alkylidene- and arylideneaminooxy at C-6, have been synthesized as a class of potential pro-drugs of autitumor agents, 5-fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (Ftorafur). Antitumor activity of these compounds against leukemia P388 or L1210 in mice and antifungal activity against Botrytis cinerea are described.

著者

Kiyofumi Inamoto

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.61, no.10, pp.987-996, 2013-10-01 (Released:2013-10-01)

参考文献数

70

被引用文献数

5 17

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Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon–hydrogen bond (C–H) functionalization/intramolecular carbon–heteroatom (nitrogen or sulfur) bond formation process. By this C–H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C–H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus.

著者

Shigeo Yasuda Haruna Yokosawa Chisato Mukai

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.64, no.7, pp.805-810, 2016-07-01 (Released:2016-07-01)

参考文献数

28

被引用文献数

2 3

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Treatment of the allenylazetidine–alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C–C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.

著者

室伏 良信 木村 美佐子 桑野 晴光 飯島 康輝 山崎 光郎 金子 正勝

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.10, pp.3760-3769, 1988-10-25

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Addition reactions of the C^<4′>-C^<5′> double bond of griseolic acid were investigated. C^<4′>-C^<5′>Dihydrogrisiolic acid was obtained by reduction of the adduct having halogen at the 4′-position.The ring juncture of the two five-membered rings of the C^<4′>-C^<5′> dihydro derivaticves was of all-"cis"configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1′-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C^<4′>-C^<5′> cis dihydrogriseolic acid derivative was weaker than that of griseolic acid.The uracil derivative of C^<4′>-C^<5′> cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3′, 5′-cyclic monophosphate (cAMP) and guanosine 3′, 5′-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C^<4′>-C^<5′>trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.

著者

杉本 和朗 大木 貞雄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1375-1378, 1964-11-25 (Released:2008-03-31)

被引用文献数

1 1

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Aromatic nitrogen mustards containing an azo group (VII∼XV), a nitrogen mustard with a carrier and masking group, were synthesized in one step starting from p-amino-phenylalanine or aliphatic p-amino-phenyl acid.

著者

佐々木 正 源 勝麿

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1329-1338, 1964-11-25 (Released:2008-03-31)

被引用文献数

12 14

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Im Rahmen der Untersuchungen der Synthesemoglichkeit von as-Triazin-N-oxyden, oxydierten wir 3-Amino- bzw. 3-Amino-5, 6-dimethyl-as-triazin durch Persaure, wobei sich die entsprechenden 5-Oxo-verbindungen und ein Mono-N-oxyd von 3-Amino-5, 6-dimethyl-as-triazin erhalten lieβen, deren Konstitutionen bzw. diejenigen der acetylierten Korpern durch Dipolmoment-Messungen sowie spektroskopisch diskutiert wurden.

著者

津田 恭介 生熊 晋 河村 正朗 太刀川 隆治 酒井 浄 田村 千尋 甘粕 治

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.12, no.11, pp.1357-1374, 1964-11-25 (Released:2008-03-31)

被引用文献数

126 208

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The structures of both tetrodonic acid hydrobromide and 6, 11-diacetylanhydrotetrodotoxin hydroiodide were established by chemical and X-ray crystallographical research. Based upon structures of both these salts and upon other chemical information, we determined that tetrodotoxin and anhydrotetrodotoxin have zwitterionic hemilactal structures.

著者

Kengo Hanaya Kazuaki Matsumoto Yuta Yokoyama Junko Kizu Mitsuru Shoji Takeshi Sugai

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.65, no.2, pp.194-199, 2017-02-01 (Released:2017-02-01)

参考文献数

14

被引用文献数

1

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Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

著者

白石 忠義 亀山 啓司 今井 直博 堂本 剛史 勝見 郁男 渡辺 清

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.3, pp.974-981, 1988-03-25

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A series of α-cyanocinnamamide derivatives was synthesized and evaluated for inhibitory activity against tyrosine-specific protein kinase using intact plasma membrane fractions from an epidermoid carcinoma cell line, A-431 cells. Among these compounds, several novel α-cyano-4-hydroxy-3,5-disubstituted cinnamamide derivatives, e.g., α-cyano-3-ethoxy-4-gtdrixt-5-phenyl-thiomethylcinnamamide (ST 638), showed potent inhibitory activity. The studies on the structure-activity relationship revealed that the presence of the hydroxy group at the 4 position and the double bond in the α-cyano-4-hydroxycinnamamide skeleton was important for potent inhibitory activity, and that the presence of hydrophobic groups at the 3 and 5 positions on the benzene ring also enhanced the inhibitory activity of α-cyano-4-hydroxycinnamamide derivatives.

著者

瀬尾 量 鶴岡 道雄 橋本 強 藤永 稔夫 小田切 優樹 上釜 兼人

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.1, pp.286-291, 1983-01-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

48 62

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Inclusion complex formations of spironolactone (SP) with three cyclodextrins (α-, β-, γ-CyDs) in aqueous solution and in the solid state were studied by the solubility method, by spectroscopic methods (UV, CD, IR) and by X-ray diffractometry, and their modes of interaction were assessed. The solid complexes of SP with β- and γ-CyDs were obtained in molar ratios of 1 : 2 and 2 : 3, respectively, and their dissolution, membrane permeation and oral absorption properties were examined. The rates of dissolution and permeation through a cellophane membrane in water were significantly increased by inclusion complexation (γ-CyD complex>β-CyD complex>SP alone), depending upon the solubility of the test samples. The serum levels of SP following oral administration of CyD complexes were found to be greater than those after administration of SP alone. The results indicated that the γ-CyD complex rather than β-CyD complex may have great utility as a faster dissolving form of SP able to produce higher serum levels.

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.