P4 and P1' optimization of bicycloproline P2 bearing tetrapeptidyl alpha-ketoamides as HCV protease inhibitors

Bioorganic & Medicinal Chemistry Letters
Yvonne YipShu-Hui Chen

Abstract

With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a.

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Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Yvonne YipShu-Hui Chen
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Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Jason LamarShu-Hui Chen
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Citations

Sep 22, 2010·Chemical Communications : Chem Comm·Anass ZnabetEelco Ruijter
Aug 26, 2014·Organic Chemistry Frontiers : an International Journal of Organic Chemistry·Tryfon Zarganes-Tzitzikas, Alexander Dömling
Dec 7, 2018·Medicinal Research Reviews·Muhammad Usman AshrafSafee Ullah Chaudhary
Sep 24, 2020·European Journal of Medicinal Chemistry·Jiang LiuVadim A Soloshonok
Jan 22, 2009·Journal of Medicinal Chemistry·Francisco VelázquezF George Njoroge
Feb 7, 2009·Journal of Medicinal Chemistry·Kevin X ChenF George Njoroge

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