The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new -nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine -nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine -nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine -nucleoside.
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http://dx.doi.org/10.3390/molecules26082341 | DOI Listing |
J Vet Intern Med
January 2025
Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany.
Background: Myxomatous mitral valve disease (MMVD) is frequently diagnosed in small breed dogs. Pimobendan oral solution has been developed to improve dosing accuracy in small and toy breed dogs.
Hypothesis/objectives: Demonstrate bioequivalence of pimobendan oral solution with pimobendan chewable tablets using a pharmacokinetic and a pharmacodynamic study in healthy purpose bred dogs.
Int J Mol Sci
December 2024
Bioinformatics and Molecular Design Research Center (BMDRC), Incheon 21983, Republic of Korea.
Understanding drug-target interactions is crucial for identifying novel lead compounds, enhancing efficacy, and reducing toxicity. Phenotype-based approaches, like analyzing drug-induced gene expression changes, have shown effectiveness in drug discovery and precision medicine. However, experimentally determining gene expression for all relevant chemicals is impractical, limiting large-scale gene expression-based screening.
View Article and Find Full Text PDFBioorg Med Chem
February 2025
Tsukuba Research Center, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
NLRP3 inflammasome inhibitor is a highly attractive drug target for the treatment of various inflammatory diseases. Here, we report the discovery of pyridazine derivatives as a new class of scaffold for NLRP3 inflammasome inhibitors. We optimized HTS hit 2a to improve both in vitro IL-1β inhibitory activity and the mean photo effect (MPE) value in the in vitro 3T3 neutral red uptake (NRU) phototoxicity test.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Medicinal Chemistry, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, PR China; Chongqing Key Laboratory of Quality Control and Safety Evaluation of APIs, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:
Fibroblast growth factor receptor 4 (FGFR4) has been proven to be a promising target for FGFR-driven HCC therapy. Great efforts have been devoted to the discovery of FGFR4 inhibitors. In this article, a new class of Ponatinib-based N-phenylpyridine-2-amine derivatives was designed and synthesized as covalent and irreversible FGFR4 selective inhibitors through a rational drug design strategy.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:
Over the past two decades, small molecules bearing [5,6]-bicyclic nitrogen-containing cores have emerged as one of the most extensively studied structures for the development of selective c-MET kinase inhibitors. Structure-activity relationship (SAR) studies have demonstrated that modifying these cores can significantly impact the biological properties of c-MET inhibitors, including safety/toxicity, potency, and metabolic stability. For example, although c-MET kinase inhibitors containing the [1,2,4]triazolo[4,3-b][1,2,4]triazine scaffold (core P) exhibit high inhibitory potency, they often face challenges due to metabolic stability defects.
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