The discovery of a novel, potent and selective beta(3)-adrenergic receptor (AR) agonist is described. SAR studies demonstrated the structural requirements for activity and selectivity. Compound 1c, which showed good beta(3)-AR activity and selectivity, was identified and pharmacokinetics were investigated.
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http://dx.doi.org/10.1016/j.bmcl.2004.11.001 | DOI Listing |
Nat Prod Bioprospect
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
Fifteen novel carbazole alkaloids, euchrestifolines A-O (1-15), were obtained from Murraya euchrestifolia. Their structures were elucidated by spectroscopic analysis, Mosher's ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A-C (1-3) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D-F (4-6) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (7) features a unique benzopyranocarbazole skeleton.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
The death signaling complex comprising extrasynaptic NMDAR and TRPM4 plays a pivotal role in the pathogenesis of ischemic stroke. Targeting the protein-protein interactions between NMDAR and TRPM4 represents a promising therapeutic strategy for ischemic stroke. Herein, we describe the discovery of a novel series of NMDAR/TRPM4 interaction interface inhibitors aimed at enhancing neuroprotective efficacy and optimizing pharmacokinetic profiles.
View Article and Find Full Text PDFAppl Environ Microbiol
December 2024
Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
In confronting the significant challenge posed by multidrug-resistant (MDR) pathogens, particularly methicillin-resistant (MRSA), the development of innovative anti-infective strategies is essential. Our research focuses on sortase A (SrtA), a vital enzyme for anchoring surface proteins in . We discovered that plantamajoside (PMS), a phenylpropanoid glycoside extracted from .
View Article and Find Full Text PDFJ Virol
December 2024
Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, USA.
Unlabelled: Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral intervention.
View Article and Find Full Text PDFJ Org Chem
January 2025
Evotec (US) Inc., 303B College Road East, Princeton, New Jersey 08540, United States.
A novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an S1 approach is reported in this study. The method allows for the preparation of highly functionalized compounds with exceptional diastereomeric selectivities and consistently reproducible yields. These compounds are of significant interest due to their remarkable biological activities toward influenza endonuclease.
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