维甲类化合物构象的同效性研究

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维甲类化合物构象的同效性研究

郭宗儒, 刘全志, 王敏敏

中国医学科学院中国协和医科大学药物研究所, 北京 100050

收稿日期:1997-06-14 修回日期:1997-09-15 出版日期:1997-12-15 发布日期:1997-12-15

Study on the Equivalent Conformation of Retinoids

Zong-Ru Guo, Quan-Zhi Liu, Min-Min Wang

Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050

Received:1997-06-14 Revised:1997-09-15 Online:1997-12-15 Published:1997-12-15

摘要/Abstract

摘要： 具有诱导细胞分化作用及癌和皮肤病化学治疗作用的维甲类化合物, 不仅要求分子一端有疏水性、另一端为极性羧基和整个分子的共轭性, 而且分子的构象也起重要作用。本文合成的N-(4-羧基-苯基)-3,5-双叔丁基-4-羟基苯甲酰胺(2)具有与全反式维甲酸(ATRA,1)相似性质的基团配置和构象,表现有维甲酸的生物活性。然而N-甲基化合物3, 由于构象的完全不同, 丧失了活性。用X线晶体学、紫外和核磁共振等方法研究了化合物2、3和ATRA的结构异同。

关键词: 维甲类化合物, 诱导细胞分化, 构象同效性

Abstract: N-(4-Carboxy-phenyl)-3,5-di-t-butyl-4-hydroxy-benzamide (2) possesses structural prerequisite for cell-differentiation inducing activity, which constitutes the therapeutic basis of all-trans-retinoic acid (ATRA) and analogues for the treatment of cancer and dermatosis. In addition to the similarity of the disposition of functional groups with ATRA, 2 shows a conformational equivalence to ATRA in terms of molecular shape, size, as well as the spatial arrangement of functional groups. However, the N-methylated compound (3) is devoid of the activity. It owes the biological behavior to the conformational difference, because of the steric interference between N-methyl group and the hydrogen atom of a phenyl ring. X-ray crystallography, UV, and NMR were performed to investigate the difference.

Key words: Retinoids, Cell-differentiation inducing activity, Conformational equivalence

Supporting: ^*Project supported by the National Natural Science Foundation of China, No. 3943013.

郭宗儒, 刘全志, 王敏敏. 维甲类化合物构象的同效性研究[J]. .

Zong-Ru Guo, Quan-Zhi Liu, Min-Min Wang. Study on the Equivalent Conformation of Retinoids[J]. .

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