The microwave-assisted aromatization method has been used for the synthesis of a series of novel thieno[2,3-c]pyridines. This rapid method produces compounds in good yield within minutes in comparison with conventional heating method. The synthesized molecules have been evaluated as a potential new series of allosteric enhancers acting at the adenosine A(1) receptor. In a functional assay, one compound (3h) showed activity comparable with that of reference compound PD 81,723.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2006.08.041 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of Brain-Penetrative Negative Allosteric Modulators of NMDA Receptors Using FEP-Guided Structure Optimization and Membrane Permeability Prediction.
J Chem Inf Model
January 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, Shandong, China.
-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role in brain disorders. Specifically, GluN2A-containing NMDA receptors have emerged as a potential therapeutic target for the treatment of depressive disorders and epilepsy. However, the development of GluN2A-containing NMDA receptor-selective antagonists, represented by -(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) and its derivatives, faces a significant challenge due to their limited ability to penetrate the blood-brain barrier (BBB), hampering their characterization and further advancement.
View Article and Find Full Text PDFDesign, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFAPH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus.
ChemMedChem
January 2025
CBS: Centre de Biologie Structurale, ABCIS, 29 rue de Navacelles, 34090, Montpellier, FRANCE.
Aminoglycoside-phosphotransferases (APHs) are a class of bacterial enzymes that mediate acquired resistance to aminoglycoside antibiotics. Here we report the identification of small molecules counteracting aminoglycoside resistance in Enterococcus casseliflavus. Molecular dynamics simulations were performed to identify an allosteric pocket in three APH enzymes belonging to 3' and 2'' subfamilies in which we then screened, in silico, 12,000 small molecules.
View Article and Find Full Text PDFNovel Orthosteric/Allosteric Ligands of Cannabinoid Receptors: An Unexpected Pharmacological Profile.
J Med Chem
January 2025
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
The design of dualsteric/bitopic receptor ligands as compounds capable of simultaneously interacting with both the orthosteric and an allosteric binding site has gained importance to achieve enhanced receptor specificity and minimize off-target effects. In this work, we reported the synthesis and biological evaluation of a new series of compounds, namely, the series, obtained by chemically combining the CB1R ago-positive allosteric modulators (PAM) with the cannabinoid receptors (CBRs) orthosteric agonist . Therefore, compounds were designed as dualsteric/bitopic ligands for CB1R with the aim of obtaining stronger CB1R agonists or ago-PAMs, with improved receptor subtype selectivity and reduction of central side effects.
View Article and Find Full Text PDFRanking Single Fluorescent Protein-Based Calcium Biosensor Performance by Molecular Dynamics Simulations.
J Chem Inf Model
January 2025
Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956, Turkey.
Genetically encoded fluorescent biosensors (GEFBs) have become indispensable tools for visualizing biological processes A typical GEFB is composed of a sensory domain (SD) that undergoes a conformational change upon ligand binding or enzymatic reaction; the SD is genetically fused with a fluorescent protein (FP). The changes in the SD allosterically modulate the chromophore environment whose spectral properties are changed. Single fluorescent (FP)-based biosensors, a subclass of GEFBs, offer a simple experimental setup; they are easy to produce in living cells, structurally stable, and simple to use due to their single-wavelength operation.
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!