We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as improved in vitro metabolic stability.
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http://dx.doi.org/10.1016/j.bmcl.2009.09.068 | DOI Listing |
World J Gastroenterol
January 2025
Department of Biochemistry, School of Medicine, College of Medicine, China Medical University, Taichung 404328, Taiwan.
This article discusses the recent study written by Koizumi . Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, which is driven by complex mechanisms, including lipid accumulation, apoptosis, and inflammatory responses exacerbated by gut barrier dysfunction. The study explored the therapeutic potential of elafibranor, a dual peroxisome proliferator-activated receptor alpha/delta agonist.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:
Cholestatic liver disease (CLD) represents a significant and growing public health concern, and there is a lack of effective therapeutic drug in clinical practice. Peroxisome proliferator-activator receptors α/δ (PPARα/δ) are regarded as potential therapeutic targets for CLD. In this study, a series of novel imidazolidinone PPARα/δ agonists were developed, and the preferred compound 8 displayed potent and well-balanced agonistic activity.
View Article and Find Full Text PDFPharmacol Res
January 2025
Gill Institute for Neuroscience, United States; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, United States. Electronic address:
Δ-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured autaptic hippocampal neurons express all of these, illustrating the rich functional and temporal heterogeneity of CB1 at a single set of synapses.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
National Center for Natural Products Research, University of Mississippi, University, Mississippi 38677, United States.
Cannabinoid receptor 1 (CB1R) has been extensively studied as a potential therapeutic target for various conditions, including pain management, obesity, emesis, and metabolic syndrome. Unlike orthosteric agonists such as Δ-tetrahydrocannabinol (THC), cannabidiol (CBD) has been identified as a negative allosteric modulator (NAM) of CB1R, among its other pharmacological targets. Previous computational and structural studies have proposed various binding sites for CB1R NAMs.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
College of Korean Medicine, Gachon University, Seongnam, 13120, South Korea. Electronic address:
Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.
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