2. Academic Validation
  3. Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor

Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor

  • ACS Med Chem Lett. 2017 Jun 29;8(7):771-774. doi: 10.1021/acsmedchemlett.7b00211.
Kyle Parcella 1,  Kyle Eastman 1,  Kap-Sun Yeung 1,  Katharine A Grant-Young 1,  Juliang Zhu 1,  Tao Wang 1,  Zhongxing Zhang 1,  Zhiwei Yin 1,  Dawn Parker 1,  Kathy Mosure 1,  Hua Fang 1,  Ying-Kai Wang 1,  Julie Lemm 1,  Xiaoliang Zhuo 1,  Umesh Hanumegowda 1,  Mengping Liu 1,  Karen Rigat 1,  Maria Donoso 1,  Maria Tuttle 1,  Tatyana Zvyaga 1,  Zuzana Haarhoff 1,  Nicholas A Meanwell 1,  Matthew G Soars 1,  Susan B Roberts 1,  John F Kadow 1
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
PMID: 28740615 DOI: 10.1021/acsmedchemlett.7b00211
Abstract

Iterative structure-activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described.

Keywords

Hepatitis C virus; NS5B polymerase; azabenzofuran; deuterium; metabolic stability; primer grip.

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