NONCALCEMIC, ANTIPROLIFERATIVE, TRANSCRIPTIONALLY ACTIVE, 24-FLUORINATED HYBRID ANALOGS OF THE HORMONE 1-ALPHA,25-DIHYDROXYVITAMIN D-3 - SYNTHESIS AND PRELIMINARY BIOLOGICAL EVALUATION

Authors
POSNER GH LEE JK WANG Q PELEG S BURKE M BREM H DOLAN P KENSLER TW
Citation
Gh. Posner et al., NONCALCEMIC, ANTIPROLIFERATIVE, TRANSCRIPTIONALLY ACTIVE, 24-FLUORINATED HYBRID ANALOGS OF THE HORMONE 1-ALPHA,25-DIHYDROXYVITAMIN D-3 - SYNTHESIS AND PRELIMINARY BIOLOGICAL EVALUATION, Journal of medicinal chemistry, 41(16), 1998, pp. 3008-3014
Citations number
35
Categorie Soggetti
Chemistry Medicinal
Journal title
Journal of medicinal chemistry → ACNP
ISSN journal
00222623
Volume
41
Issue
16
Year of publication
1998
Pages
3008 - 3014
Database
ISI
SICI code
0022-2623(1998)41:16<3008:NATA2>2.0.ZU;2-B
Abstract
Four new hybrid analogues of 1 alpha,25-dihydroxyvitamin D-3 (1) have been synthesized in a convergent manner by joining A-ring and C,D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side cha in, was designed to be lipophilic and inert toward 24-hydroxylase enzy me catabolism. Each hybrid analogue with 1 beta,3 alpha-substituent st ereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically d esirable combination of in vitro high antiproliferative activity in tw o different cell lines and high transcriptional activity with also low calcemic activity in vivo.