ArticleJournal of medicinal chemistry2014
Diarylureas as allosteric modulators of the cannabinoid CB1 receptor: structure-activity relationship studies on 1-(4-chlorophenyl)-3-{3-[6-(pyrrolidin-1-yl)pyridin-2-yl]phenyl}urea (PSNCBAM-1).
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 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
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- Development of Squaramides as Allosteric Modulators of the CBJournal of medicinal chemistry · 2025Article
- Discovery and Characterization of the First Nonpeptide Antagonists for the Relaxin-3/RXFP3 System.Journal of medicinal chemistry · 2022Article
- Development of 3-(4-Chlorophenyl)-1-(phenethyl)urea Analogues as Allosteric Modulators of the Cannabinoid Type-1 Receptor: RTICBM-189 is Brain Penetrant and Attenuates Reinstatement of Cocaine-Seeking Behavior.Journal of medicinal chemistry · 2022Article
- Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids.Bioorganic & medicinal chemistry · 2021Article
- Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development.Journal of medicinal chemistry · 2021Review
- Structural Optimization of the Diarylurea PSNCBAM-1, an Allosteric Modulator of Cannabinoid Receptor 1.Current therapeutic research, clinical and experimental · 2020Article
- Allosteric Modulation of Cannabinoid Receptor 1-Current Challenges and Future Opportunities.International journal of molecular sciences · 2019Review
- Synthesis and Pharmacological Evaluation of 1-Phenyl-3-Thiophenylurea Derivatives as Cannabinoid Type-1 Receptor Allosteric Modulators.Journal of medicinal chemistry · 2019Article
- Selective modulation of the cannabinoid type 1 (CBMedChemComm · 2019Review
- Structural Insights into CB1 Receptor Biased Signaling.International journal of molecular sciences · 2019Review
- Translational potential of allosteric modulators targeting the cannabinoid CBActa pharmacologica Sinica · 2019Review
- Diarylureas Containing 5-Membered Heterocycles as CBACS chemical neuroscience · 2019Article
- Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development.Current topics in medicinal chemistry · 2019Review
- Pyrimidinyl Biphenylureas Act as Allosteric Modulators to Activate Cannabinoid Receptor 1 and InitiateMolecular pharmacology · 2019Article
- Allosteric modulators of cannabinoid receptor 1: developing compounds for improved specificity.Drug metabolism reviews · 2018Review
- Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor.Bioorganic & medicinal chemistry · 2017Article
- Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists.ACS chemical neuroscience · 2017Article
- The great divide: Separation between in vitro and in vivo effects of PSNCBAM-based CBNeuropharmacology · 2017Article
- Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.Neuropharmacology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The recent discovery of allosteric modulators of the CB1 receptor including PSNCBAM-1 (4) has generated significant interest in CB1 receptor allosteric modulation. Here in the first SAR study on 4, we have designed and synthesized a series of analogs focusing on modifications at two positions. Pharmacological evaluation in calcium mobilization and binding assays revealed the importance of alkyl substitution at the 2-aminopyridine moiety and electron deficient aromatic groups at the 4-chlorophenyl position for activity at the CB1 receptor, resulting in several analogs with comparable potency to 4. These compounds increased the specific binding of [(3)H]CP55,940, in agreement with previous reports. Importantly, 4 and two analogs dose-dependently reduced the Emax of the agonist curve in the CB1 calcium mobilization assays, confirming their negative allosteric modulator characteristics. Given the side effects associated with CB1 receptor orthosteric antagonists, negative allosteric modulators provide an alternative approach to modulate the pharmacologically important CB1 receptor.
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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.