Discovery of ASP5286: A novel non-immunosuppressive cyclophilin inhibitor for the treatment of HCV.

Discovery of ASP5286: A novel non-immunosuppressive cyclophilin inhibitor for the treatment of HCV. Bioorg Med Chem Lett. 2020 Aug 15;30(16):127308 Authors: Makino T, Yoshimura S, Neya M, Yamanaka T, Sawada M, Tsujii E, Barrett D Abstract Evidence indicates that hepatitis C virus (HCV) utilizes cellular cyclophilin proteins in its replication, and cyclophilin inhibitors represent a new class of anti-HCV agents. We have established an efficient synthetic methodology to generate FR901459 derivatives via N, O-acyl migration reaction while avoiding total synthesis. Through a detailed structure-activity relationship study, we improved anti-HCV activity while decreasing immunosuppressive activity. Additionally, we discovered the importance of substitution at the 3 position for not only improving anti-HCV activity but also pharmacokinetic profile. Finally, by striking an appropriate balance between potency, solubility, and permeability, we discovered ASP5286 (13) as a potential clinical candidate for anti-HCV therapy. PMID: 32631528 [PubMed - in process]
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research