A-ring hydroxymethyl 19-nor analogs of the natural hormone 1α,25-dihydroxyvitamin D3: Synthesis and preliminary biological evaluation

Mark A. Hatcher; Sara Peleg; Patrick Dolan; Thomas W. Kensler; Amy Sarjeant; Gary H. Posner

doi:10.1016/j.bmc.2005.04.010

A-ring hydroxymethyl 19-nor analogs of the natural hormone 1α,25-dihydroxyvitamin D₃: Synthesis and preliminary biological evaluation

Mark A. Hatcher, Sara Peleg, Patrick Dolan, Thomas W. Kensler, Amy Sarjeant, Gary H. Posner

Bloomberg School of Public Health

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

13 Scopus citations

Abstract

A series 5-8 of 1- and 3-CH₂OH 19-nor analogs of the hormone calcitriol (1) has been prepared. Surprisingly, 19-nor 1α-CH₂OH analog 5a is more antiproliferative at 100 nM concentration than the corresponding regioisomeric analog 6a with the natural 1α-OH group, and 1α-CH₂OH hybrid analog 7a is similar in antiproliferative potency to calcitriol (1) even at low nanomolar concentrations.

Original language	English (US)
Pages (from-to)	3964-3976
Number of pages	13
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.bmc.2005.04.010
State	Published - Jun 2 2005

Keywords

19-Nor
Calcitriol
Hydroxymethyl A-ring
Novel analogs

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2005.04.010

Cite this

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title = "A-ring hydroxymethyl 19-nor analogs of the natural hormone 1α,25-dihydroxyvitamin D3: Synthesis and preliminary biological evaluation",

abstract = "A series 5-8 of 1- and 3-CH2OH 19-nor analogs of the hormone calcitriol (1) has been prepared. Surprisingly, 19-nor 1α-CH2OH analog 5a is more antiproliferative at 100 nM concentration than the corresponding regioisomeric analog 6a with the natural 1α-OH group, and 1α-CH2OH hybrid analog 7a is similar in antiproliferative potency to calcitriol (1) even at low nanomolar concentrations.",

keywords = "19-Nor, Calcitriol, Hydroxymethyl A-ring, Novel analogs",

author = "Hatcher, {Mark A.} and Sara Peleg and Patrick Dolan and Kensler, {Thomas W.} and Amy Sarjeant and Posner, {Gary H.}",

note = "Funding Information: We thank the NIH for financial support (CA 93547).",

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T1 - A-ring hydroxymethyl 19-nor analogs of the natural hormone 1α,25-dihydroxyvitamin D3

T2 - Synthesis and preliminary biological evaluation

AU - Hatcher, Mark A.

AU - Peleg, Sara

AU - Dolan, Patrick

AU - Kensler, Thomas W.

AU - Sarjeant, Amy

AU - Posner, Gary H.

N1 - Funding Information: We thank the NIH for financial support (CA 93547).

PY - 2005/6/2

Y1 - 2005/6/2

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AB - A series 5-8 of 1- and 3-CH2OH 19-nor analogs of the hormone calcitriol (1) has been prepared. Surprisingly, 19-nor 1α-CH2OH analog 5a is more antiproliferative at 100 nM concentration than the corresponding regioisomeric analog 6a with the natural 1α-OH group, and 1α-CH2OH hybrid analog 7a is similar in antiproliferative potency to calcitriol (1) even at low nanomolar concentrations.

KW - 19-Nor

KW - Calcitriol

KW - Hydroxymethyl A-ring

KW - Novel analogs

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