New Synthetic Vitamin D Analogs with Antiproliferative Activities

Andreas      Steinmeyer; Gerald      Kirsch; Gunter      Neef; Katica      Schwarz

doi:10.2174/1381612003400470

Abstract

The introduction of oxygen atoms into different positions of the vitamin D side chain is described. By combining the arising 23-oxa and 25-oxa elements with other structural modifications (19-nor, iso-19-nor, 20-methyl, 20-ene, 20,21-cyclo) calcitriol analogs with remarkable levels of dissociation between beneficial acitivities on cell growth regulation and undesired hypercalcemia were identified. Structure-activity relations are elaborated in a very systematic outline of the Schering drug finding program in this particular class of vitamin D compounds.

Keywords: Antiproliferative Activities, 23 Oxa Calcitriols, 19 Nor 23 oxa Calcitriols, Iso 19 nor 23 oxa Calcitriols, 20 Methyl 23 oxa calcitriols, 20 Ene 23 oxa Calcitriol, 20 Ene 19 nor 23 oxa Calcitriols, 20 21 Cyclo 23 oxa calcitriols, 25 oxa Calcitriols, Relative binding affinity, Vitamin D receptor, 1 4 Diazabicyclo 2 2 2 octane, Diisobutylaluminum hydride, Vitamin D binding prtien, Human leukemia cell line, Lithium diisopropylamide