Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1α,25-dihydroxyvitamin D3. Synthesis and preliminary biological evaluation

Gary H. Posner; Jae Kyoo Lee; Qiang Wang; Sara Peleg; Martin Burke; Henry Brem; Patrick Dolan; Thomas W. Kensler

doi:10.1021/jm980031t

Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1α,25-dihydroxyvitamin D₃. Synthesis and preliminary biological evaluation

Gary H. Posner, Jae Kyoo Lee, Qiang Wang, Sara Peleg, Martin Burke, Henry Brem, Patrick Dolan, Thomas W. Kensler

Research output: Contribution to journal › Article › peer-review

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Abstract

Four new hybrid analogues of 1α,25-dihydroxyvitamim D₃ (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 chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with lβ,3α-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.

Original language	English (US)
Pages (from-to)	3008-3014
Number of pages	7
Journal	Journal of medicinal chemistry
Volume	41
Issue number	16
DOIs	https://doi.org/10.1021/jm980031t
State	Published - Jul 30 1998

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Posner, G. H., Lee, J. K., Wang, Q., Peleg, S., Burke, M., Brem, H., Dolan, P., & Kensler, T. W. (1998). Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1α,25-dihydroxyvitamin D₃. Synthesis and preliminary biological evaluation. Journal of medicinal chemistry, 41(16), 3008-3014. https://doi.org/10.1021/jm980031t

Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1α,25-dihydroxyvitamin D₃. Synthesis and preliminary biological evaluation. / Posner, Gary H.; Lee, Jae Kyoo; Wang, Qiang et al.
In: Journal of medicinal chemistry, Vol. 41, No. 16, 30.07.1998, p. 3008-3014.

Research output: Contribution to journal › Article › peer-review

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abstract = "Four new hybrid analogues of 1α,25-dihydroxyvitamim D3 (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 chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with lβ,3α-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.",

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AU - Brem, Henry

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AU - Kensler, Thomas W.

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Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1α,25-dihydroxyvitamin D₃. Synthesis and preliminary biological evaluation

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