Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1alpha,25-dihydroxyvitamin D3: cis-perhydrindane CE-ring analogues.
The synthesis and biological activity of novel CD-ring modified analogues of 22-oxa-1alpha,25-dihydroxyvitamin D(3), lacking the D-ring and featuring a connection between C-12 and C-21 (cis-perhydrindane CE-ring analogues), is described. The synthesis of the CE-ring system follows Meyers' methodology for the preparation of enantiomerically pure hydrinden-2-ones. The analogues show a complete lack of binding affinity for the vitamin D receptor (pig nVDR) and of antiproliferative activity (MCF-7 cells), as compared to calcitriol.
Demin
Samuël
S
Department of Organic Chemistry, Ghent University, Krijgslaan 281 S4, B-9000 Gent, Belgium.
Van Haver
Dirk
D
Vandewalle
Maurits
M
De Clercq
Pierre J
PJ
Bouillon
Roger
R
Verstuyf
Annemieke
A
D001943:Breast Neoplasms; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002117:Calcitriol