ArticleBioorganic & medicinal chemistry letters2013
Structure activity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan (NAQ) analogues as potent opioid receptor ligands: preliminary results on the role of electronic characteristics for affinity and function.
Article in Bioorganic & medicinal chemistry letters, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed.
- 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
- Role of mu opioid receptor (MOR) agonist efficacy as a determinant of opioid antinociception in a novel assay of pain-depressed behavior in female and male mice.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Role of Efficacy as a Determinant of Locomotor Activation by Mu Opioid Receptor Ligands in Female and Male Mice.The Journal of pharmacology and experimental therapeutics · 2022Article
- An Integrated Approach toward NanoBRET Tracers for Analysis of GPCR Ligand Engagement.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
- Manipulating Pharmacodynamic Efficacy with Agonist + Antagonist Mixtures: In Vitro and In Vivo Studies with Opioids and Cannabinoids.The Journal of pharmacology and experimental therapeutics · 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
- 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
- Determinants of opioid abuse potential: Insights using intracranial self-stimulation.Peptides · 2019Review
- In vitro and in vivo functional profile characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) as a low efficacy mu opioid receptor modulator.European journal of pharmacology · 2018Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan (NAQ) was previously designed following the 'message-address' concept and was identified as a potent and highly selective mu opioid receptor (MOR) ligand based on its pharmacological profile. We here report the preliminary structure activity relationship (SAR) studies of this novel lead compound. For the new ligands synthesized as NAQ analogues, their binding assay results showed that a longer spacer and a saturated ring system of the side chain were unfavorable for their MOR selectivity over the kappa and delta opioid receptors. In contrast, substitutions with different electronic properties at either 1'- or 4'-position of the isoquinoline ring of the side chain were generally acceptable for reasonable MOR selectivity. The majority of NAQ analogues retained low efficacy at the MOR compared to NAQ in the (35)S-GTP[γS] binding assays while electron-withdrawing groups at 1'-position of the isoquinoline ring induced higher MOR stimulation than electron-donating groups did. In summary, the electronic characteristics of substituents at 1'- or 4'-position of the isoquinoline ring in NAQ seem to be critical and need to be further tuned up to achieve higher MOR selectivity and lower MOR stimulation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.