Studies on Antidiabetic Agents. X. Synthesis and Biological Activities of Pioglitazone and Related Compounds
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概要
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Various analogues of a new antidiabetic agent, pioglitazone (AD-4833,U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4-thiazolidinediones (I), thia-analogues of pioglitazone, were prepared via Meerwein arylation of teh alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene)-2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKA^y) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4-thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and teh benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed.
- 社団法人日本薬学会の論文
- 1991-06-25
著者
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池田 衡
丸石製薬株式会社中央研究所
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目黒 寛司
浜理薬品工業株式会社
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左右田 隆
武田薬品工業株式会社医薬研究本部
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百瀬 裕
Research and Development Division, Takeda Chemical Industries, Ltd.
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目黒 寛司
Research and Development Division, Takeda Chemical Industries, Ltd
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池田 衡
Research and Development Division, Takeda Chemical Industries, Ltd
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畑中 千年
Research and Development Division, Takeda Chemical Industries, Ltd
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大井 悟
Research and Development Division, Takeda Chemical Industries, Ltd
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左右田 隆
Research and Development Division, Takeda Chemical Industries, Ltd
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畑中 千年
Research And Development Division Takeda Chemical Industries Ltd
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Ikeda H
Fukuoka Univ. Fukuoka Jpn
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百瀬 裕
Research And Development Division Takeda Chemical Industries Ltd.
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Sohda T
Takeda Chemical Industries Ltd. Pharmaceutical Research Division
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大井 悟
Research And Development Division Takeda Chemical Industries Ltd
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