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Ectonucleotidase inhibitors: an updated patent review (2017-2023).
Expert Opin Ther Pat
November 2024
Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.
Article Synopsis
- The main enzymes responsible for breaking down nucleotides at the cell surface are NTPDases, ENPPs, alkaline phosphatases, and e5'NT, which can influence various health conditions like cancer and inflammation, making them potential therapeutic targets.
- This review focuses on ectonucleotidase inhibitors, including both nucleoside/nucleotide analogues and bicyclic compounds, that have been patented between 2017 and 2023, highlighting their chemistry and clinical applications.
- The review emphasizes the importance of nucleotides in regulating key physiological processes and discusses the therapeutic potential of small molecules that affect ectonucleotidase activity, including advancements in combination therapy and selectivity.
Characterisation of ten NS2B-NS3 proteases: Paving the way for pan-flavivirus drugs.
Antiviral Res
June 2024
Research School of Chemistry, Australian National University, Canberra, ACT, 2601, Australia. Electronic address:
Flaviviruses can cause severe illness in humans. Effective and safe vaccines are available for some species; however, for many flaviviruses disease prevention or specific treatments remain unavailable. The viral replication cycle depends on the proteolytic activity of the NS2B-NS3 protease, which releases functional viral proteins from a non-functional polyprotein precursor, rendering the protease a promising drug target.
View Article and Find Full Text PDFSynthesis and applications of cyclonucleosides: an update (2010-2023).
Mol Divers
October 2024
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106, Warsaw, Poland.
Cyclonucleosides are a group of nucleoside derivatives which, in addition to the classical N-glycosidic bond, have an additional covalent bond (linker, bridge) in their structure, which connects the heterocyclic base and sugar ring. The majority of them have been discovered in the laboratory; however, few such compounds have also been found in natural sources, including metabolites of sponges or radical damage occurring in nucleic acids. Due to their structural properties-rigid, fixed conformation-they have found wide applications in medicinal chemistry and biochemistry as biocides as well as enzyme inhibitors and molecular probes.
View Article and Find Full Text PDFTotal Synthesis of Nikkomycin S and Nikkomycin So.
Org Lett
November 2023
State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.
The nikkomycins S/So are a class of locked nucleoside antibiotics that share a common [5,6] -bicyclic core. Herein we present an efficient synthesis of these nikkomycins from diene, using neighboring group participation -glycosylation and stereoselective oxidation state installation. This synthetic strategy overcomes several challenges due to the poor redox tolerance of the uracil base, the high strain of the -fused furanopyran C8 monosaccharides, and the acid-sensitive glycosidic bond when dealing with the deoxynucleotide natural product nikkomycin S.
View Article and Find Full Text PDFStructure activity relationships of 5-HT and 5-HT serotonin receptor antagonists: N, C2 and 5'-Modified (N)-methanocarba-adenosine derivatives.
Eur J Med Chem
November 2023
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address:
(N)-Methanocarba adenosine derivatives were structurally modified to target 5-HT serotonin receptors as antagonists, predominantly containing branched N-alkyl groups. N-Dicycloalkyl-methyl groups, including their asymmetric variations, as well as 2-iodo, were found to generally favor 5-HTRs, while only N-dicyclohexyl-methyl derivative 35 showed weak 5-HTR affinity (K 3.6 μM).
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