2α-修饰对1α-羟基维生素D3-26,23-内酯的维生素D受体拮抗活性具有显著影响。

Remarkable effect of 2[small alpha]-modification on the VDR antagonistic activity of 1small alpha-hydroxyvitamin D3-26,23-lactones.

作者信息

Saito Nozomi, Matsunaga Toshihiro, Fujishima Toshie, Anzai Miyuki, Saito Hiroshi, Takenouchi Kazuya, Miura Daishiro, Ishizuka Seiichi, Takayama Hiroaki, Kittaka Atsushi

机构信息

Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa 199-0195, Japan.

出版信息

Org Biomol Chem. 2003 Dec 21;1(24):4396-402. doi: 10.1039/b311107e. Epub 2003 Nov 6.

DOI:10.1039/b311107e

PMID:14685312

Abstract

Novel 2[small alpha]-methyl-, 2[small alpha]-(3-hydroxypropyl)- and 2[small alpha]-(3-hydroxypropoxy)-substituted 25-dehydro-1[small alpha]-hydroxyvitamin D-26,23-lactone derivatives were efficiently synthesized Reformatsky type allylation and palladium-catalyzed alkenylative cyclization processes, and their biological activities were evaluated. Introducing functional groups into the 2[small alpha]-position of the vitamin D-26,23-lactones resulted in remarkable enhancement of their antagonistic activity on vitamin D receptor (VDR).

摘要

通过Reformatsky型烯丙基化反应和钯催化的烯基化环化反应高效合成了新型的2[小α]-甲基、2[小α]-(3-羟丙基)和2[小α]-(3-羟丙氧基)取代的25-脱氢-1[小α]-羟基维生素D-26,23-内酯衍生物，并对其生物活性进行了评估。在维生素D-26,23-内酯的2[小α]位引入官能团导致其对维生素D受体（VDR）的拮抗活性显著增强。