著者

山下 純一 武田 節夫 松本 宏 采見 憲男 安本 三治

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.35, pp.2373-2381, 1987

被引用文献数

1

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Various O-alkoxyalkyl derivatives of 2'-deoxy-5-trifluoroniethyluridine(F_3Thd) were synthesized, and the antitumor activities of the compounds against sarcoma 180 were examined by oral administration to mice. Among the formal-type derivatives, 3',5'-di-O-ethoxymethyl (3), 3',5'-di-O-benzyloxyinethyl (12), 5'-O-benzyloxymethyl (13) and 3'-O-benzyloxymethyl (14) compounds showed high activities, which were six-fold higher than that of F_3Thd itself. Since acetal-type derivatives were unstable under acidic conditions, antitumor testing of the compounds was also carried out with co-administration of sodium bicarbonate. 5 '-O-(1-Ethoxypropyl)-F_3Thd (25) and 5'-O-(1-benz:yloxypropyl)-F_3Thd (37) showed the highest activities among the acetal-type derivatives, but the ED_50 values of the compounds were not lower than those of effective formal-type compounds. These O-alkoxyalkyl derivatives of F_3Thd are resistant to degradation by thymidine phosphorylase and are activated by microsornal drug-metabolizing enzymes after absorption.

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

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

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.