Synthesis, Conformational Analysis, and Biological Evaluation of 19-nor-Vitamin D3 Analogues with A-Ring Modifications

被引：17
|
作者：
Sanchez-Abella, Laura [1 ,2 ]
Fernandez, Susana [1 ,2 ]
Verstuyf, Annemieke [3 ]
Verlinden, Lieve [3 ]
Gotor, Vicente [1 ,2 ]
Ferrero, Miguel [1 ,2 ]
机构：
[1] Univ Oviedo, Dept Quim Organ & Inorgan, E-33006 Oviedo, Asturias, Spain
[2] Univ Oviedo, Inst Univ Biotecnol Asturias, E-33006 Oviedo, Asturias, Spain
[3] Katholieke Univ Leuven, Lab Expt Geneeskunde & Endocrinol, B-3000 Louvain, Belgium
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 19期
关键词：
1-ALPHA; 25-DIHYDROXY-19-NORVITAMIN D-3; EFFICIENT SYNTHESIS; DERIVATIVES; ACID;
D O I：
10.1021/jm900711d
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We have synthesized several isomers of 19-nor-vitamin D analogues possessing a hydroxy group at C-2 as well as novel derivatives bearing an epoxy substituent at the A-ring. All vitamins were prepared in convergent syntheses utilizing the modified Julia olefination. 1 alpha,2 alpha,25-Trihydroxy-19-nor-vitamin D-3 (3) and 2 beta,3 beta-epoxy-1 alpha,25-dihydroxy-3-deoxy-19-nor-vitamin D-3 (10), which showed the highest affinity to the vitamin D receptor, displayed the highest potency among the tested compounds to inhibit the proliferation of MCF-7 breast cancer cells.
引用
收藏
页码：6158 / 6162
页数：5
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