Low-calcemic, efficacious, 1alpha,25-dihydroxyvitamin D3 analog QW-1624F2-2: calcemic dose-response determination, preclinical genotoxicity testing, and revision of A-ring stereochemistry

Based on an X-ray crystal structure determination, the A-ring stereochemistry of hybrid analog QW-1624F2-2 (1alpha-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3) is revised to be 1alpha-CH2OH-3beta-OH. This analog is shown to be approximately 80-100 times less calciuric tha...

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Veröffentlicht in:	Steroids 2004-10, Vol.69 (11-12), p.757-762
Hauptverfasser:	Posner, Gary H, Jeon, Heung Bae, Sarjeant, Amy, Riccio, Edward S, Doppalapudi, Rupa S, Kapetanovic, Izet M, Saha, Uttam, Dolan, Patrick, Kensler, Thomas W
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Bone Marrow Cells - metabolism Calcitriol - analogs & derivatives Calcitriol - chemistry Calcium - metabolism CHO Cells Cricetinae Crystallography, X-Ray Dose-Response Relationship, Drug Escherichia coli - metabolism Mice Micronucleus Tests Models, Chemical Models, Molecular Mutation Receptors, Calcitriol - metabolism Salmonella - metabolism Stereoisomerism
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Zusammenfassung:	Based on an X-ray crystal structure determination, the A-ring stereochemistry of hybrid analog QW-1624F2-2 (1alpha-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3) is revised to be 1alpha-CH2OH-3beta-OH. This analog is shown to be approximately 80-100 times less calciuric than the natural hormone 1alpha,25-dihydoxyvitamin D3. This analog is shown also to be non-genotoxic in three different standard assays.
ISSN:	0039-128X