Imidazolidine-4-thiones have been suggested as potential prebiotic organocatalysts for light-driven α-alkylations of aldehydes by bromoacetonitrile. However, imidazolidine-4-thiones react with bromoacetonitrile to give -cyanomethylated dihydroimidazoles. Kinetic studies show that enamines derived from these cyclic secondary amines and aldehydes are more nucleophilic than enamines derived from aldehydes and MacMillan organocatalysts.
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http://dx.doi.org/10.1039/d3cc01912h | DOI Listing |
J Comput Chem
January 2025
Department of Organic Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Lipophilicity and acidity/basicity are fundamental physical properties that profoundly affect the compound's pharmacological activity, bioavailability, metabolism, and toxicity. Predicting lipophilicity, measured by (1-octanol-water distribution coefficient logarithm), and acidity/basicity, measured by (negative of acid ionization constant logarithm), is essential for early drug discovery success. However, the limited availability of experimental data and poor accuracy of standard and assessment methods for saturated fluorine-containing derivatives pose a significant challenge to achieving satisfactory results for this compound class.
View Article and Find Full Text PDFOrg Lett
December 2024
School of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China.
Using a SbCl/O mild oxidation system, a dual functionalization of the α,β-C-H bonds in alanine ester derivatives was achieved via enamine-imine tautomerism, and a series of quinoline-4-carboxylates were synthesized through a fragmentation-reassembly pathway. The investigation of the substrate scope revealed that various functional groups were easily tolerated, highlighting that this reaction provided an efficient path for the construction of the quinoline-4-carboxylate framework.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35233, United States.
Proinflammatory TREM1 receptors expressed on myeloid-derived cells have recently been recognized as a new oncogenic target in cancer, including gliomas. They are established chemotherapeutic targets in neurodegenerative Parkinson's and Alzheimer's diseases, and they also contribute to stroke and sepsis severities. TREM1 activation requires the TREM1/DAP12 interaction for receptor clustering and signal transduction coordinated by TREM1 ligands.
View Article and Find Full Text PDFCell Chem Biol
November 2024
Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany. Electronic address:
J Med Chem
November 2024
Enamine Ltd., Winston Churchill Street 78, 02094 Kyiv, Ukraine.
Proline analogues are versatile chemical building blocks that enable modular construction of small-molecule drugs and pharmaceutical peptides. Over the past 15 years, the FDA has approved over 15 drugs containing proline analogues in their structures, five in the last three years alone (daridorexant, trofinetide, nirmatrelvir, rezafungin, danicopan). This perspective offers an analysis of the most common types of proline analogues currently trending in drug design.
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