Synthesis and biological properties of 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones--weak agonists.

Bioorganic & Medicinal Chemistry
Grazia ChielliniHector F DeLuca

Abstract

In a continuing effort to explore the 2-methylene-1alpha-hydroxy-19-norvitamin D(3) class of pharmacologically important vitamin D compounds, two novel 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones, GC-3 and HLV, were synthesized and biologically tested. Based on reports of similarly structured molecules, it was hypothesized that these compounds might act as antagonists, at least in vitro. The pathway designed to synthesize these compounds was based on two key steps: first, the Lythgoe-type Wittig-Horner coupling of Windaus-Grundmann-type ketone 18, with phosphine oxide 15, followed, later in the synthesis, by the Zn-mediated Reformatsky-type allylation of aldehyde 20 with methylbromomethylacrylate 8. Our biological data show that neither compound has antagonistic activity but acts as weak agonists in vitro and in vivo.

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Citations

Nov 18, 2015·Journal of Medicinal Chemistry·Izabela Karolina SibilskaHector Floyd Deluca
Dec 24, 2015·Organic & Biomolecular Chemistry·Urszula KuleszaRafal R Sicinski
Jul 28, 2020·Pharmaceuticals·Susana Fernández, Miguel Ferrero
Sep 16, 2014·Journal of Medicinal Chemistry·Izabela K SibilskaHector F DeLuca
Jun 9, 2020·Journal of Medicinal Chemistry·Izabela K Sibilska-KaminskiHector F DeLuca

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