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Synthesis of deuterium‐, tritium‐, and carbon‐14‐labeled BILN2061, a potent hepatitis C virus protease inhibitor
Author(s) -
Latli Bachir,
Hrapchak Matt,
Gorys Vida,
Busacca Carl A.,
Senanayake Chris
Publication year - 2005
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.940
Subject(s) - chemistry , thiourea , tritium , isopropyl , stereochemistry , hepatitis c virus , carbon 14 , specific activity , radiochemistry , virus , biochemistry , medicinal chemistry , enzyme , virology , organic chemistry , physics , quantum mechanics , nuclear physics , biology
Hepatitis C virus (HCV) serine protease is a target for antiviral therapy against HCV infection, a leading cause of liver transplantation in the US. BILN2061, (1 S , 4 R , 6 S , 7 Z , 14 S , 18 R )‐14‐cyclopentyloxycarbonylamino‐18‐[2‐(2‐isopropylamino‐thiazol‐4‐yl)‐7‐methoxyquinolin‐4‐yloxy]‐2,15‐dioxo‐3,16‐diazatricyclo[14.3.0.0 4,6 ]nonadec‐7‐ene‐4‐carboxylic acid, is a potent inhibitor of HCV and the first compound in this class of cyclic peptides in human trials. Here, we report the synthesis of deuterium‐labeled BILN2061 with isotopic enrichment of 99%, tritium‐labeled BILN2061 with a specific activity of 17.1 GBq/mmol, and carbon‐14‐labeled BILN2061 with a specific activity of 1.83 GBq/mmol. The isotopes were incorporated via a Hantzsch thiazole synthesis of labeled isopropyl thiourea and α ‐bromoketone intermediate. The preparation of labeled isopropyl thiourea is reported. Copyright © 2005 John Wiley & Sons, Ltd.