活性维生素D3类似物的合成及构效关系研究

胡代花; 陈旺; 王永吉

doi:10.7536/PC151226

化学进展 ›› 2016, Vol. 28 ›› Issue (6) :839-859 DOI: 10.7536/PC151226

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活性维生素D₃类似物的合成及构效关系研究

胡代花, 陈旺, 王永吉*

作者信息 +

Synthesis and Structure-Activity Relationship of Active Vitamin D₃ Analogues

Hu Daihua, Chen Wang, Wang Yongji*

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文章历史 +

摘要

1α,25-二羟基维生素D₃(1α,25-(OH)₂-D₃,125D)是维生素D中最具生理活性的代谢产物,但因高钙血症副反应而限制其临床应用。从对构效关系的研究出发,迄今已合成三千多种类似物。本文综述了近年来对某些A环修饰(C2位修饰、C3位修饰、芳香A环类似物、A环开环类似物)、侧链修饰、CD环修饰、seco-B环修饰和非开环甾体的活性维生素 D₃ 类似物的设计、合成以及构效关系的研究,旨在为新型较佳活性维生素D₃类似物的合成及临床开发提供参考。

Abstract

1α,25-Dihydroxyvitamin D₃(1α,25-(OH)₂-D₃, 125D)is the most active metabolite of vitamin D₃, but the therapeutic application of 125D is limited by induction of hypercalcemia. The need for vitamin D compounds with selective biological profiles has stimulated the synthesis of more than three thousand analogues of 125D. This article reviews the recent progress of vitamin D research in the design and synthesis of the structural modifications in the A ring (including modification in the C2-, and C3-substitued, aromatic A ring and seco-A ring analogues), side chain, CD ring, seco-B ring, and non-secosteroidal vitamin D₃ analogs, and the relation between the structure and the biological activities.

Contents
1 Introduction
2 Structure-activity relationship of analogues modified in the A ring
2.1 Analogues modification of C-2-substitued
2.2 Aromatic A-ring 125D analogues
2.3 Ring-A-seco-19-nor analogues
2.4 C-3-subtitued-25-hydroxy analogues
3 Structure-activity relationship of analogues modified in the side chains
3.1 26-Desmethyl-2-methylene-22-ene-19-nor-analogues
3.2 C-22-oxa-analogues
3.3 Analogues with aromatic side chains attached at C-17
3.4 C-2 substituted analogues having ringed side chains
3.5 Analogues of combination of triple bond and adamantane ring on the side chain
4 Structure-activity relationship of analogues modified in CD-ring
4.1 13α-Substituted-des-C-ring-19-nor-125D analogues
4.2 Analogues with α-hydroxyalkyl substituents at C12
4.3 9-Alkylidene-19-nor-125D analogues with unnatural triene system
5 Structure-activity relation of analogues modified substituted in seco-B ring
5.1 6-Substituted analogues of 125D
5.2 C-7-methyl-19-nor-125D analogues
6 Structure-activity relationship of non-secosteroidal vitamin D analogues
6.1 Bis- and tris-aromatic analogues
6.2 p-Carborane-based non-secosteroidal vitamin D analogues
7 Conclusion and outlook

关键词

1α,25-二羟基维生素D₃ / 类似物 / 构效关系 / 化学合成 / 生物活性

Key words

1α,25-dihydroxyvitamin D₃ / analogues / structure-activity relationship / chemical synthesis / biological activities

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胡代花, 陈旺, 王永吉. 活性维生素D₃类似物的合成及构效关系研究[J]. 化学进展, 2016, 28(6): 839-859 DOI:10.7536/PC151226

Hu Daihua, Chen Wang, Wang Yongji. Synthesis and Structure-Activity Relationship of Active Vitamin D₃ Analogues[J]. Progress in Chemistry, 2016, 28(6): 839-859 DOI:10.7536/PC151226

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Received	Published	Revised
2015-12-01	2016-06-15	2016-02-01
Online Date
2016-03-23

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