Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluation.
Three new Vitamin D analogs 3-5 incorporating a -CHF(2) group as an -OH surrogate have been prepared. Two of these new analogs (3 and 5) are strongly antiproliferative toward murine keratinocytes and are approximately 50 times less calciuric in vivo than the natural hormone calcitriol. The transcriptional activity of the 25-CHF(2) analog 3 is higher than that of the 1-CHF(2) analog 4.
Posner
Gary H
GH
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA. ghp@jhu.edu
Suh
Byung Chul
BC
Petersen
Kimberly S
KS
Dolan
Patrick
P
Agoston
Elin S
ES
Kensler
Thomas W
TW
Koh
John T
JT
Peleg
Sara
S
D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000652:urine; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D005461:Fluorine / Q000737:chemistry*; D006728:Hormones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D001688:Biological Products; D006728:Hormones; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D005461:Fluorine; D002118:Calcium