Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

New derivatives of 1alpha,25-dihydroxy-19-norvitamin D3 with two substituents at C-2: synthesis and biological activity.

Shimizu M, Iwasaki Y, Shimazaki M, Amano Y, Yamamoto K, Reischl W, Yamada S

Laboratory of Medicinal Chemistry, School of Biomedical Science, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan. shimizu.mr@tmd.ac.jp

To examine the effect of 2,2-disubstitution on the biological activities of 19-norvitamin D analogs, novel 2,2-disubstituted-(20R)- and (20S)-1alpha,25-dihydroxy-19-norvitamin D3 analogs were prepared and their biological activities were studied. All the synthesized analogs possessing hydrophobic 2alpha-substituents were more active than the corresponding 2beta-isomers both in binding to the vitamin D receptor and in activating gene transcription. The 2alpha-methyl-2beta-hydroxy analog 9b was found to have markedly higher transcriptional activity (32-fold) than the natural ligand 1a, although the two had the same binding affinity to the vitamin D receptor. To our knowledge, this analog is among the most potent of 19-norvitamin D analogs.

Published 16 February 2005 in Bioorg Med Chem Lett, 15(5): 1451-5.
Full-text of this article is available online (may require subscription).

© 2004-2008 Vitamin D Research Today. All Rights Reserved.