1130802-07-1Relevant articles and documents
Structure-activity relationship (SAR) development and discovery of potent indole-based inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase
Chen, Kevin X.,Vibulbhan, Bancha,Yang, Weiying,Sannigrahi, Mousumi,Velazquez, Francisco,Chan, Tin-Yau,Venkatraman, Srikanth,Anilkumar, Gopinadhan N.,Zeng, Qingbei,Bennet, Frank,Jiang, Yueheng,Lesburg, Charles A.,Duca, Jose,Pinto, Patrick,Gavalas, Stephen,Huang, Yuhua,Wu, Wanli,Selyutin, Oleg,Agrawal, Sony,Feld, Boris,Huang, Hsueh-Cheng,Li, Cheng,Cheng, Kuo-Chi,Shih, Neng-Yang,Kozlowski, Joseph A.,Rosenblum, Stuart B.,Njoroge, F. George
, p. 754 - 765 (2012/03/11)
Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2, extensive SAR studies were performed at different positions of the indole core. The best C-5 groups were found to be compact and nonpolar moieties and that the C-6 attachments were not affecting potency. Limited N-1 benzyl-type substituent studies indicated that the best substitutions were fluoro or methyl groups at 2′ or 5′ positions of the benzyl group. To improve pharmacokinetic (PK) properties, acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the identification of compound 56, which had an excellent potency in both NS5B enzyme (IC50 = 0.008 μM) and cell-based replicon (EC50 = 0.02 μM) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 μM?h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported.
SUBSTITUTED INDOLE DERIVATIVES AND METHODS OF USE THEREOF
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Page/Page column 159-160, (2009/04/25)
The present invention relates to Substituted Indole Derivatives, compositions comprising at least one Substituted Indole Derivative, and methods of using these Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.
