A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB(2) agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB(2) receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB(2) agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2009.10.062 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Early Evaluation of the Interaction and Gender Differences in Combination of Apatinib and Metoprolol Using Humanized CYP2D6 Model.
Chem Res Toxicol
January 2025
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P.R. China.
Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood.
View Article and Find Full Text PDFHow Should We Use Hyaluronidase for Dissolving Hyaluronic Acid Fillers?
J Cosmet Dermatol
January 2025
Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea.
Background: Hyaluronic acid (HA) fillers are commonly used in esthetic medicine for facial contouring and rejuvenation. However, complications such as overcorrection, vascular occlusion, and irregular filler distribution necessitate the use of hyaluronidase to dissolve the fillers. This study aimed to evaluate the efficacy of hyaluronidase in degrading different types of HA fillers and provide clinical guidelines for its use based on filler type, dosage, and application techniques.
View Article and Find Full Text PDFAntiamnesic and Neurotrophic Effects of (Jacq.) R. Br (Fabaceae) Aqueous Extract on In Vivo and In Vitro Models of Excitotoxicity.
Behav Neurol
January 2025
Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon.
Amnesia is a memory disorder marked by the inability to recall or acquire information. Hence, drugs that also target the neurogenesis process constitute a hope to discover a cure against memory disorders. This study is aimed at evaluating the antiamnesic and neurotrophic effects of the aqueous extract of () on in vivo and in vitro models of excitotoxicity.
View Article and Find Full Text PDFRegulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses.
iScience
January 2025
Department of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.
The regulation of cellular metabolism is crucial for cell survival, with Sch9 in serving a key role as a substrate of TORC1. Sch9 localizes to the vacuolar membrane through binding to PI(3,5)P, which is necessary for TORC1-dependent phosphorylation. This study demonstrates that cytosolic pH regulates Sch9 localization.
View Article and Find Full Text PDFProspects of elafibranor in treating alcohol-associated liver diseases.
World J Gastroenterol
January 2025
School of Basic Medicine, Qilu Medical University, Zibo 255300, Shandong Province, China.
Alcohol-related liver disease (ALD), which is induced by excessive alcohol consumption, is a leading cause of liver-related morbidity and mortality. ALD patients exhibit a spectrum of liver injuries, including hepatic steatosis, inflammation, and fibrosis, similar to symptoms of nonalcohol-associated liver diseases such as primary biliary cholangitis, metabolic dysfunction-associated steatotic liver disease, and nonalcoholic steatohepatitis. Elafibranor has been approved for the treatment of primary biliary cholangitis and has been shown to improve symptoms in both animal models and cell models of metabolic dysfunction-associated steatotic liver disease and nonalcoholic steatohepatitis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!