Highly antiproliferative, low-calcemic, side-chain amide and hydroxamate analogs of the hormone 1alpha,25-dihydroxyvitamin D3.
Four new side-chain amide (2 and 3) and hydroxamate (4 and 5) analogs of the hormone calcitriol (1) have been prepared. Even though lacking the 25-OH group characteristic of natural calcitriol (1), analogs 2-4 are as antiproliferative in vitro as calcitriol (1) but are 20-40 times less calciuric in vivo than calcitriol (1).
Sinishtaj
Sandra
S
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
Jeon
Heung Bae
HB
Dolan
Patrick
P
Kensler
Thomas W
TW
Posner
Gary H
GH
D000577:Amides / Q000737:chemistry*; D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006877:Hydroxamic Acids / Q000737:chemistry*; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D006877:Hydroxamic Acids; D002117:Calcitriol; D002118:Calcium