ArticleBioorganic & medicinal chemistry2013
Binding mode characterization of 6α- and 6β-N-heterocyclic substituted naltrexamine derivatives via docking in opioid receptor crystal structures and site-directed mutagenesis studies: application of the 'message-address' concept in development of mu opioid receptor selective antagonists.
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Discovery of 6α-Thiazolylcarboxamidonaltrexamine Derivative (NTZ) as a Potent and Central Nervous System Penetrant Opioid Receptor Modulator with Drug-like Properties for Potential Treatment of Opioid Use Disorder.ACS pharmacology & translational science · 2024Article
- Blocking potential metabolic sites on NAT to improve its safety profile while retaining the pharmacological profile.Bioorganic chemistry · 2024Article
- Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors.Molecules (Basel, Switzerland) · 2024Article
- Design, Synthesis, and Biological Evaluation of NAP Isosteres: A Switch from Peripheral to Central Nervous System Acting Mu-Opioid Receptor Antagonists.Journal of medicinal chemistry · 2022Article
- Exploring naltrexamine derivatives featuring azaindole moiety via nitrogen-walk approach to investigate their in vitro pharmacological profiles at the mu opioid receptor.Bioorganic & medicinal chemistry letters · 2021Article
- Computational insights into the molecular mechanisms of differentiated allosteric modulation at the mu opioid receptor by structurally similar bitopic modulators.Journal of computer-aided molecular design · 2020Article
- Characterization of 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN) as a Novel Opioid Receptor Modulator for Opioid Use Disorder Treatment.ACS chemical neuroscience · 2019Article
- Structure-Activity Relationship Studies of 6α- and 6β-Indolylacetamidonaltrexamine Derivatives as Bitopic Mu Opioid Receptor Modulators and Elaboration of the "Message-Address Concept" To Comprehend Their Functional Conversion.ACS chemical neuroscience · 2019Article
- Role of mu-opioid agonist efficacy on antinociceptive interactions between mu agonists and the nociceptin opioid peptide agonist Ro 64-6198 in rhesus monkeys.European journal of pharmacology · 2019Article
- Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.ACS chemical neuroscience · 2018Article
- Binding mode analyses of NAP derivatives as mu opioid receptor selective ligands through docking studies and molecular dynamics simulation.Bioorganic & medicinal chemistry · 2017Article
- Design, synthesis, and characterization of rhein analogs as novel inhibitors of scavenger receptor A.Bioorganic & medicinal chemistry letters · 2017Article
- 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4'-pyridylcarboxamido)morphinan (NAP) Modulating the Mu Opioid Receptor in a Biased Fashion.ACS chemical neuroscience · 2016Article
- Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan analogues as opioid receptor ligands.Bioorganic & medicinal chemistry · 2015Article
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7 authors at 1 institution in 1 country.
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Abstract
Highly selective opioid receptor antagonists are essential pharmacological probes in opioid receptor structural characterization and opioid agonist functional studies. Currently, there is no highly selective, nonpeptidyl and reversible mu opioid receptor antagonist available. Among a series of naltrexamine derivatives that have been designed and synthesized, two compounds, NAP and NAQ, were previously identified as novel leads for this purpose based on their in vitro and in vivo pharmacological profiles. Both compounds displayed high binding affinity and selectivity to the mu opioid receptor. To further study the interaction of these two ligands with the three opioid receptors, the recently released opioid receptor crystal structures were employed in docking studies to further test our original hypothesis that the ligands recognize a unique 'address' domain in the mu opioid receptor involving Trp318 that facilitates their selectivity. These modeling results were supported by site-directed mutagenesis studies on the mu opioid receptor, where the mutants Y210A and W318A confirmed the role of the latter in binding. Such work not only enriched the 'message-address' concept, also facilitated our next generation ligand design and development.
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