[6,7]-heterocycle-fused 14-hydroxymorphinan derivatives: design, synthesis, and opioid receptor activity.
A series of new 14-hydroxymorphinan analogues with a thiazole or imidazo[2,1-b]thiazole fragment as the heterocyclic function fused to ring C were designed and synthesized. These compounds can be viewed as the result of a direct modification at ring C of the 14-hydroxymorphinan scaffold. Among these compounds, three were identified as having potent binding affinity (approximately 1 nM) at both kappa and mu receptors, and acting as agonists at kappa and partial agonists or antagonists at mu receptors. In view of the promising results from studies on compounds with mixed kappa and mu receptor activities, these new compounds warrant further investigation.
Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, 555 Zuchongzhi Road, Shanghai 201203, China.
Fuying
F
Li
Chenlei
C
Yin
Jie
J
Chen
Jinggen
J
Liu
Xin
X
Xie
Ao
A
Zhang
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009019:Morphinans / Q000737:chemistry* / Q000494:pharmacology*; D009292:Narcotic Antagonists; D011485:Protein Binding; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid