title: Syntheses and receptor-binding studies of derivatives of the opioid antagonist naltrexone.
abstract: Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for mu-receptors and its derivatives have been notable as novel receptor antagonists. In this paper, the preparation of several naltrexone derivatives is described; these were used to investigate the role of the oxygenated functional groups in facilitating binding to a series of the opioid receptors. The derivatives showed affinity for opioid mu-receptors which was similar to that of naltrexone, but these compounds, which had masked hydroxyl functional groups, displayed a moderate activity. These results suggest that every oxygenated functional group in naltrexone (1) plays an important role in binding to the opioid receptor.
authors.affiliation: Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, 981-8558 Sendai, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uwai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kabuto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D001921:Brain / Q000378:metabolism; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D006168:Guinea Pigs; D008024:Ligands; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry; D009292:Narcotic Antagonists / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone