A-ring hydroxymethyl 19-nor analogs of the natural hormone 1alpha,25-dihydroxyvitamin D(3): synthesis and preliminary biological evaluation.
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.
Hatcher
Mark A
MA
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
Peleg
Sara
S
Dolan
Patrick
P
Kensler
Thomas W
TW
Sarjeant
Amy
A
Posner
Gary H
GH
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
D000970:Antineoplastic Agents; D002117:Calcitriol