Mackman, Richard L.; Steadman, Victoria A.; Dean, David K.; Jansa, Petr; Poullennec, Karine G.; Appleby, Todd; Austin, Carol; Blakemore, Caroline A.; Cai, Ruby; Cannizzaro, Carina; Chin, Gregory; Chiva, Jean-Yves C.; Dunbar, Neil A.; Fliri, Hans; Highton, Adrian J.; Hui, Hon; Ji, Mingzhe; Jin, Haolun; Karki, Kapil; Keats, Andrew J.; Lazarides, Linos; Lee, Yu-Jen; Liclican, Albert; Mish, Michael; Murray, Bernard; Pettit, Simon B.; Pyun, Peter; Sangi, Michael; Santos, Rex; Sanvoisin, Jonathan; Schmitz, Uli; Schrier, Adam; Siegel, Dustin; Sperandio, David; Stepan, George; Tian, Yang; Watt, Gregory M.; Yang, Hai; Schultz, Brian E. published the artcile< Discovery of a potent and orally bioavailable cyclophilin inhibitor derived from the sanglifehrin macrocycle>, Synthetic Route of 552331-06-3, the main research area is cyclic peptidomimetic total synthesis orally bioavailable cyclophilin inhibitor; drug discovery antihepatitis C virus agent structure activity; isoquinoline peptide Stille coupling hydrolysis reduction vinylation RCM macrolactamization; mol docking crystal structure.
Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead (I) derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor (II). The macrocycle ring size was reduced by one atom, and an internal hydrogen bond drove improved permeability and drug-like properties. II demonstrates potent Cyp inhibition (Kd = 5 nM), potent anti-HCV 2a activity (EC50 = 98 nM), and high oral bioavailability in rat (100%) and dog (55%). The synthetic accessibility and properties of II support its potential as an anti-HCV agent and for interrogating the role of Cyp inhibition in a variety of diseases.
Journal of Medicinal Chemistry published new progress about Anti-hepatitis C virus agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem