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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

C-20 Cyclopropyl Vitamin D3 Analogs

Author(s): Milan R. Uskokovic, Percy Manchand, Stanislaw Marczak, Hubert Maehr, Pawel Jankowski, Luciano Adorini and G. Satyanarayana Reddy

Volume 6 , Issue 12 , 2006

Page: [1289 - 1296] Pages: 8

DOI: 10.2174/156802606777864962

Price: $65

Abstract

The formal C-20 methylation of 1,25-dihydroxy vitamin D3 (calcitriol) and bridging of two methyl groups produces spiro[cyclopropane-1, 20-calcitriol], colloquially referred to as C-20 cyclopropylcalcitriol, which is much more active in MLR for suppression of interferon-γ release than calcitriol, and hypercalcemia in mice is elicited at a ten-fold lower dose when compared to calcitriol. Introduction of the Δ16,17-double bond, modification of the side chain by 23- unsaturation and replacement of the methyl groups at C-26 and C-27 with trifluoromethyl moieties create a highly active series of vitamin D analogs. As previously observed in the calcitriol series, the presence of the C-16 double bond in the cyclopropyl analogs also arrests metabolic side-chain oxidation in the at the C-24 oxo level in UMR 106 cells. The enhanced biological activity is ascribed, at least in part, to the improved resistance toward metabolic degradation.

Keywords: hydrogenation, Transactivation, Prostate tumor, UMR 106 cells, 20-cyclopropyl analogs


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