Biomaterial Database

Effect of removal of the 14-hydroxy group on the affinity of the 4,5-epoxymorphinan derivatives for orexin and opioid receptors. 2022

Koki Katoh, and Naoshi Yamamoto, and Yukiko Ishikawa, and Yoko Irukayama-Tomobe, and Ryuji Tanimura, and Tsuyoshi Saitoh, and Yasuyuki Nagumo, and Noriki Kutsumura, and Masashi Yanagisawa, and Hiroshi Nagase

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.

To investigate the contribution of hydrogen bonding between the 14-hydroxy group and the 6-amide chain on the binding affinity of nalfurafine toward KOR and OX1R, we prepared the 14-H and 14-dehydrated nalfurafine and their five-membered D-ring nalfurafine (D-nor-nalfurafine) derivatives. The 14-H and 14-dehydrated nalfurafine derivatives showed almost the same affinity for KOR as nalfurafine and more potent affinity for OX1R. On the other hand, 14-H and 14-dehydrated D-nor-nalfurafine derivatives showed weak affinity for KOR and almost no affinity for OX1R. The conformational analyses suggested that the 6-amide chains of the nalfurafine derivatives are mainly oriented just at or downward from the C-ring, while those of the D-nor-nalfurafine derivatives were mainly oriented toward the upper side of the C-ring even in the absence of the 14-hydroxy group. We postulated that the ion-dipole interaction between the 6-amide and the 16-nitrogen might stabilize the upwardly oriented 6-amide group. These results suggested that the 14-hydroxy group and the ion-dipole interaction would play important roles in the orientation of the 6-amide group, which might control the affinity between KOR and OX1R.

UI	MeSH Term	Description	Entries
D009019	Morphinans	Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.	Morphinan
D011957	Receptors, Opioid	Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.	Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D057809	HEK293 Cells	A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.	293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D064446	Orexin Receptors	G-protein-coupled NEUROPEPTIDE RECEPTORS that have specificity for OREXINS and play a role in appetite control, and sleep-wake cycles. Two principle receptor types exist, each having a specificity for OREXIN A and OREXIN B peptide subtypes.	Hypocretin Receptor,OX1 Receptor,OX2 Receptor,Orexin Receptor,HCRT Receptor 1,HCRT Receptor 2,HCTR2 Protein,Hypocretin Receptor 2,Hypocretin Receptors,Hypocretin Receptors 2,Hypocretin-1 Receptor,Hypocretin-2 Receptor,OX1 Receptors,OX2 Receptors,Orexin A Receptor,Orexin B Receptor,Orexin Receptor 2,Orexin Receptor Type 1,Orexin Receptor Type 2,Orexin-A Receptor,Orexin-A Receptors,Orexin-B Receptor,Orexin-B Receptors,Receptor 2, Hypocretin,Receptor, Orexin-A,Receptor, Orexin-B,Hypocretin 1 Receptor,Hypocretin 2 Receptor,Orexin A Receptors,Orexin B Receptors,Protein, HCTR2,Receptor 1, HCRT,Receptor 2, HCRT,Receptor 2, Orexin,Receptor, Hypocretin,Receptor, Hypocretin-1,Receptor, Hypocretin-2,Receptor, OX1,Receptor, OX2,Receptor, Orexin,Receptor, Orexin A,Receptor, Orexin B,Receptors 2, Hypocretin,Receptors, Hypocretin,Receptors, OX1,Receptors, OX2,Receptors, Orexin,Receptors, Orexin-A,Receptors, Orexin-B