Investigation of Beckett-Casy model 1: synthesis of novel 16,17-seco-naltrexone derivatives and their pharmacology

Satomi Imaide; Hideaki Fujii; Akio Watanabe; Toru Nemoto; Mayumi Nakajima; Kaoru Nakao; Hidenori Mochizuki; Hiroshi Nagase

doi:10.1016/j.bmcl.2009.12.039

Investigation of Beckett-Casy model 1: synthesis of novel 16,17-seco-naltrexone derivatives and their pharmacology

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1055-8. doi: 10.1016/j.bmcl.2009.12.039. Epub 2009 Dec 26.

Authors

Satomi Imaide¹, Hideaki Fujii, Akio Watanabe, Toru Nemoto, Mayumi Nakajima, Kaoru Nakao, Hidenori Mochizuki, Hiroshi Nagase

Affiliation

¹ School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.

PMID: 20056539
DOI: 10.1016/j.bmcl.2009.12.039

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Chemistry, Pharmaceutical / methods*
Models, Molecular*
Naltrexone / analogs & derivatives
Naltrexone / chemical synthesis*
Naltrexone / pharmacology*
Structure-Activity Relationship

Substances

Naltrexone