Novel Substituted Monocyclic Heteroaryl Compounds for Treating Huntington's Disease.
Basic Information
ID: ALA4715900
Journal: ACS Med Chem Lett
Title: Novel Substituted Monocyclic Heteroaryl Compounds for Treating Huntington's Disease.
Authors: Sabnis RW
Abstract: In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4'-methoxy- and 4'-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4'-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC of 0.042 μM and produced significant cytotoxicity (CC = 0.11 μM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC = 0.73 μM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.
CiteXplore: 33488955
DOI: 10.1021/acsmedchemlett.0c00622
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