ArticleACS chemical neuroscience2019
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.
Article in ACS chemical neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Structural Determinants of μ-Opioid Receptor Antagonism and Respiratory Liability in Phenylfentanyl Analogues.ACS chemical neuroscience · 2026Article
- Investigating the Landscape of C6-Azaindole Side Chain on the Epoxymorphinan Skeleton via the Nitrogen Walk Concept: A Strategy to Enhance Drug-Like Properties.Journal of medicinal chemistry · 2026Article
- 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
- Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.Journal of medicinal chemistry · 2024Article
- Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors.Molecules (Basel, Switzerland) · 2024Article
- Research status of indole-modified natural products.RSC medicinal chemistry · 2023Review
- Merging cultures and disciplines to create a drug discovery ecosystem at Virginia commonwealth university: Medicinal chemistry, structural biology, molecular and behavioral pharmacology and computational chemistry.SLAS discovery : advancing life sciences R & D · 2023Review
- Structural Alterations of the "Address" Moiety of NAN Leading to the Discovery of a Novel Opioid Receptor Modulator with Reduced hERG Toxicity.Journal of medicinal chemistry · 2023Article
- 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
- Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.Bioorganic chemistry · 2022Article
- Biased, Bitopic, Opioid-Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Recent Chemical and Pharmacological Developments on 14-Oxygenated-Molecules (Basel, Switzerland) · 2021Review
- 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
- Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking.Molecules (Basel, Switzerland) · 2021Article
- 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.Bioorganic chemistry · 2021Article
- Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.Future medicinal chemistry · 2021Article
- Comparison of Pharmacological Properties between the Kappa Opioid Receptor Agonist Nalfurafine and 42B, Its 3-Dehydroxy Analogue: Disconnect betweenACS chemical neuroscience · 2020Article
- Kappa opioid receptors mediate an initial aversive component of paclitaxel-induced neuropathy.Psychopharmacology · 2020Article
- Identification and characterization of plant-derived alkaloids, corydine and corydaline, as novel mu opioid receptor agonists.Scientific reports · 2020Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Structure-activity relationship (SAR) studies of numerous opioid ligands have shown that introduction of a methyl or ethyl group on the tertiary amino group at position 17 of the epoxymorphinan skeleton generally results in a mu opioid receptor (MOR) agonist while introduction of a cyclopropylmethyl group typically leads to an antagonist. Furthermore, it has been shown that introduction of heterocyclic ring systems at position 6 can favor antagonism. However, it was reported that 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(2'-indolyl)acetamido]morphinan (INTA), which bears a cyclopropylmethyl group at position 17 and an indole ring at position 6, acted as a MOR agonist. We herein report a SAR study on INTA with a series of its complementary derivatives to understand how introduction of an indole moiety with α or β linkage at position 6 of the epoxymorphinan skeleton may influence ligand function. Interestingly, one of INTA derivatives, compound 15 (NAN) was identified as a MOR antagonist both in vitro and in vivo. Molecular modeling studies revealed that INTA and NAN may interact with different domains of the MOR allosteric binding site. In addition, INTA may interact with W293 and N150 residues found in the orthosteric site to stabilize MOR activation conformation while NAN does not. These results suggest that INTA and NAN may be bitopic ligands and the type of allosteric interactions with the MOR influence their functional activity. These insights along with our enriched comprehension of the "message-address" concept will to benefit future ligand design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.