Chemical Modification of Ansamitocins. III. Synthesis and Biological Effects of 3-Acyl Esters of Maytansinol
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概要
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Several semisynthetic maytansinoids that differ in the structure of the acyl group at the C_3 position were prepared by acylation of maytansinol (3) using appropriate carboxylic acids or their active derivatives, and the effects of the compounds on the growth of Tetrahymena pyriformis and the survival of tumor-bearing mice were determined. Among these analogs, the C_3 esters having a straight chain aliphatic acyl (11,12), cycloalkanecarbonyl (18-20) or phenylacetyl group (22), and those having a 2-(N-acetyl-N-methyl) aminohexanoyl (7) or (2-(N-acetyl-N-methyl) aminophenylpropionyl group (8), strongly inhibited the growth of T. pyriformis and exhibited potent activity against B16 melanoma in mice. The potencies were similar to those of maytansine and ansamitocin P-3. The most striking result was the finding that the phenylglycinate (31) was superior to maytansine in terms of its broader effective dose range against ip B16 melanoma and P388 leukemia in mice ; however, higher doses of the phenylglycinate were required.
- 社団法人日本薬学会の論文
- 1984-09-25
著者
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橋本 直人
Central Research Division Takeda Chemical Industries Ltd.
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野村 容朗
Central Research Division, Takeda Chemical Ind., Ltd.,
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大津 紘一郎
Central Research Division, Takeda Chemical Industries, Ltd.,
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香西 義雄
Central Research Division, Takeda Chemical Industries, Ltd.,
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香西 義雄
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
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野村 容朗
Research and Development Division, Eisai Company, Ltd.,
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谷田 清一
Central research Division, Takeda Chemical Ind., Ltd.
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河合 昭悦
Central Research Division, Takeda Chemical Industries, Ltd.
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秋元 浩
Central Research Division, Takeda Chemical Industries, Ltd.
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野村 容朗
Research And Development Division Eisai Company Ltd.
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谷田 清一
Central Research Division Takeda Chemical Industries Ltd.
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Nomura Hiroaki
Research And Development Division Eisai Company Ltd.
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秋元 浩
武田薬品工業(株)
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秋元 浩
武田薬品工業
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秋元 浩
武田薬品工業(株)化学研究所
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大津 紘一郎
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
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河合 昭悦
Central Research Division Takeda Chemical Industries Ltd.
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