C-20 cyclopropyl vitamin D3 analogs.
The formal C-20 methylation of 1,25-dihydroxy vitamin D3 (calcitriol) and bridging of two methyl groups produces spiro[cyclopropane-1, 20'-calcitriol], colloquially referred to as C-20 cyclopropylcalcitriol, which is much more active in MLR for suppression of interferon-gamma release than calcitriol, and hypercalcemia in mice is elicited at a ten-fold lower dose when compared to calcitriol. Introduction of the Delta16,17-double bond, modification of the side chain by 23-unsaturation and replacement of the methyl groups at C-26 and C-27 with trifluoromethyl moieties create a highly active series of vitamin D analogs. As previously observed in the calcitriol series, the presence of the C-16 double bond in the cyclopropyl analogs also arrests metabolic side-chain oxidation in the at the C-24 oxo level in UMR 106 cells. The enhanced biological activity is ascribed, at least in part, to the improved resistance toward metabolic degradation.
Uskokovic
Milan R
MR
BioXell, Inc., Nutley, NJ 07110, USA.
Manchand
Percy
P
Marczak
Stanislaw
S
Maehr
Hubert
H
Jankowski
Pawel
P
Adorini
Luciano
L
Reddy
G Satyanarayana
GS
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002762:Cholecalciferol