155732-90-4Relevant articles and documents
Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4′-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors
Huang, Boshi,Gunta, Rama,Wang, Huiqun,Li, Mengchu,Cao, Danni,Mendez, Rolando E.,Gillespie, James C.,Chen, Chongguang,Huang, Lan-Hsuan M.,Liu-Chen, Lee-Yuan,Selley, Dana E.,Zhang, Yan
, (2021)
In the present study, the role of 3-hydroxy group of a series of epoxymorphinan derivatives in their binding affinity and selectivity profiles toward the opioid receptors (ORs) has been investigated. It was found that the 3-hydroxy group was crucial for the binding affinity of these derivatives for all three ORs due to the fact that all the analogues 1a-e exhibited significantly higher binding affinities compared to their counterpart 3-dehydroxy ones 6a-e. Meanwhile most compounds carrying the 3-hydroxy group possessed similar selectivity profiles for the kappa opioid receptor over the mu opioid receptor as their corresponding 3-dehydroxy derivatives. [35S]-GTPγS functional assay results indicated that the 3-hydroxy group of these epoxymorphinan derivatives was important for maintaining their potency on the ORs with various effects. Further molecular modeling studies helped comprehend the remarkably different binding affinity and functional profiles between compound 1c (NCP) and its 3-dehydroxy analogue 6c.
Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano) phenanthrene derivatives and their pharmacologies
Nagase, Hiroshi,Imaide, Satomi,Hirayama, Shigeto,Nemoto, Toru,Fujii, Hideaki
scheme or table, p. 5071 - 5074 (2012/08/28)
To clarify the essential structures of an opioid κ receptor selective agonist, nalfurafine, for binding to the κ receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano) phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the κ receptor. Moreover, the phenol ring was also not essential for the binding to the κ receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano)phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine.
Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives
Kubota, Hitoshi,Rothman, Richard B.,Dersch, Chris,McCullough, Karen,Pinto, Julia,Rice, Kenner C.
, p. 799 - 804 (2007/10/03)
The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable δ selectivity with that of NTI, all of the novel compounds possessed low affinity for δ receptors indicating the important role of the 3-oxygen atom of NTI for interaction with δ-opioid receptors.
