title: A-ring hydroxymethyl 19-nor analogs of the natural hormone 1alpha,25-dihydroxyvitamin D(3): synthesis and preliminary biological evaluation.
abstract: A series 5-8 of 1- and 3-CH(2)OH 19-nor analogs of the hormone calcitriol (1) has been prepared. Surprisingly, 19-nor 1alpha-CH(2)OH analog 5a is more antiproliferative at 100 nM concentration than the corresponding regioisomeric analog 6a with the natural 1alpha-OH group, and 1alpha-CH(2)OH hybrid analog 7a is similar in antiproliferative potency to calcitriol (1) even at low nanomolar concentrations.
authors.affiliation: Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hatcher
authors.forename: Sara
authors.initials: S
authors.lastname: Peleg
authors.forename: Patrick
authors.initials: P
authors.lastname: Dolan
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: Amy
authors.initials: A
authors.lastname: Sarjeant
authors.forename: Gary H
authors.initials: GH
authors.lastname: Posner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002117:Calcitriol