ArticleJournal of medicinal chemistry2014
Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology and ADME profile.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 23 citations in OpenAlex.
- Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery.Handbook of experimental pharmacology · 2022Review
- Predictive Models to Identify Small Molecule Activators and Inhibitors of Opioid Receptors.Journal of chemical information and modeling · 2021Article
- Synthesis and preliminary evaluation of 4-hydroxy-6-(3-[Bioorganic & medicinal chemistry letters · 2020Article
- Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic).Journal of medicinal chemistry · 2018Article
- Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)- N-[1 R)-1-(Cyclohexylmethyl)-2-methylpropyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (CDTic).Journal of medicinal chemistry · 2018Article
- Probing ligand recognition of the opioid pan antagonist AT-076 at nociceptin, kappa, mu, and delta opioid receptors through structure-activity relationships.Scientific reports · 2017Article
- Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of replacement of the 3-hydroxyphenyl group with pyridine or thiophene bioisosteres.Bioorganic & medicinal chemistry · 2016Article
- Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of the 3- and 4-methyl substituents.Bioorganic & medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
JDTic analogues 4-15 which have the hydroxyl groups replaced with other groups were synthesized and their in vitro efficacy at the μ, δ, and κ opioid receptors determined and compared to JDTic using [(35)S]GTPγS assays. Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and 0.041 nM compared to the Ke = 0.02 nM for JDTic at the κ receptor and were highly selective for the κ receptor relative to the μ and δ opioid receptors. Unexpectedly, replacement of the 3-hydroxyl substituent of the 4-(3-hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and selective KOR antagonists. In vitro studies to determine various ADME properties combined with calculated TPSA, clogP, and logBB values suggests that the potent and selective κ opioid receptors 4, 5, 13, and 14 deserve consideration for further development toward potential drugs for CNS disorders.
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Registered trials
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