New synthetic vitamin D analogs with antiproliferative activities.
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.
Steinmeyer
A
A
Schering AG, Institute of Medicinal Chemistry, Berlin, D-13342, Germany. andreas.steinmeyer@schering.de
Kirsch
G
G
Neef
G
G
Schwarz
K
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives*; D002455:Cell Division / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002117:Calcitriol