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Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
High potency improvements to weak aryl uracil HCV polymerase inhibitor leads
Pamela Donner1, John T Randolph, Peggy Huang
1AbbVie, Department R4AJ, Building AP52N, 1 North Waukegan Road, North Chicago, IL 60064, United States. pamela.l.donner@abbvie.com
Abstract:
Described herein is the development of a potent non-nucleoside, small molecule inhibitor of genotype 1 HCV NS5B Polymerase. A 23 μM inhibitor that was active against HCV polymerase was further elaborated into a potent single-digit nanomolar inhibitor of HCV NS5B polymerase by additional manipulation of the R and R1 substituents. Subsequent modifications to improve physical properties were made in an attempt to achieve an acceptable pharmacokinetic profile.
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