Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus
Copyright policy )Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus
Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC(50)=0.07 μM, %F=18), are reported.
- Bristol-Myers Squibb (Germany) Germany
- Bristol-Myers Squibb (United States) United States
Models, Molecular, Indoles, Molecular Structure, Hepacivirus, Viral Nonstructural Proteins, Enzyme Activation, Inhibitory Concentration 50, Structure-Activity Relationship, Heterocyclic Compounds, Drug Design
Models, Molecular, Indoles, Molecular Structure, Hepacivirus, Viral Nonstructural Proteins, Enzyme Activation, Inhibitory Concentration 50, Structure-Activity Relationship, Heterocyclic Compounds, Drug Design
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