Investigation of Beckett-Casy model 1: synthesis of novel 16,17-seco-naltrexone derivatives and their pharmacology.
Novel 16,17-seco-naltrexone derivatives 3 were synthesized using a 16-17 bond cleavage reaction of naltrexone as the key reaction to examine the Beckett-Casy model. All the prepared 16,17-seco-naltrexone derivatives 3 showed lower affinities for opioid receptors than naltrexone. Although the results of binding assay seem to support the existence of a cavity in the model, further investigation using 15,16-nornaltrexone derivatives 26 will be needed to confirm the model.
Imaide
Satomi
S
School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Fujii
Hideaki
H
Watanabe
Akio
A
Nemoto
Toru
T
Nakajima
Mayumi
M
Nakao
Kaoru
K
Mochizuki
Hidenori
H
Nagase
Hiroshi
H
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008958:Models, Molecular; D009271:Naltrexone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D009271:Naltrexone