Design, synthesis and biological evaluation of novel 1α,25-dihydroxyvitamin D3 analogues possessing aromatic ring on 2α-position

被引：31

作者：

Honzawa, S

Hirasaka, K

Yamamoto, Y

Peleg, S

Fujishima, T

Kurihara, M

Saito, N

Kishimoto, S

Sugiura, T

Waku, K

Hiroaki, TA

Kittaka, A ^{[1
]}

机构：

[1] Teikyo Univ, Fac Pharmaceut Sci, Dept Pharmaceut Chem, Sagamiko, Kanagawa 1990195, Japan

[2] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA

[3] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan

[4] Teikyo Univ, Fac Pharmaceut Sci, Dept Hyg Chem, Sagamiko, Kanagawa 1990195, Japan

来源：

TETRAHEDRON | 2005年 / 61卷 / 47期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

vitamin D receptor; aromatic ring; ligand binding domain;

D O I：

10.1016/j.tet.2005.08.116

中图分类号：

O62 [有机化学];

学科分类号：

070303 [有机化学]; 081704 [应用化学];

摘要：

In the present study, we describe the synthesis of new analogues of 1 alpha,25-dihydroxyvitamin D-3 (1), which possess hydrophobic aromatic ring on the 2 alpha. position. Among these analogues, 2a-benzy] analogue showed the highest potency in the affinity for the wild type vitamin D receptor (VDR) and induction of HL-60 cell differentiation as well as transcriptional activity. Affinity for the mutant VDR related to hereditary vitainin D-resistant rickets (R274L) was also examined. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：11253 / 11263

页数：11

共 31 条

[1]

Metabolism of 2α-propoxy-1α,25-dihydroxyvitamin D3 and 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1 [J].