2. Academic Validation
  3. Identification of a novel series of potent HCV NS5B Site I inhibitors

Identification of a novel series of potent HCV NS5B Site I inhibitors

  • Bioorg Med Chem Lett. 2014 Apr 15;24(8):1993-7. doi: 10.1016/j.bmcl.2014.02.047.
Kyle J Eastman 1,  Zhong Yang 2,  John A Bender 2,  Kathy Mosure 2,  Julie A Lemm 2,  Nicholas A Meanwell 2,  Susan B Roberts 2,  Jay Knipe 2,  John F Kadow 2
Affiliations

Affiliations

  • 1 Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: kyle.eastman@bms.com.
  • 2 Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
PMID: 24656612 DOI: 10.1016/j.bmcl.2014.02.047
Abstract

Efforts investigating spatially comparative alternates of the ethylene-bridged piperazine in BMS-791325 that would offer a maintained or improved virologic and pharmacokinetic profile have been multifaceted. One foray involved the utilization of various octahydropyrrolo[3,4-c]pyrrole propellanes. Many of the propellane analogs described in this work exhibited better than targeted potency (less than 20 nM). Additionally, improved exposure in rats was achieved through the employment of two newly invented and now readily accessible carbon bridged propellanes as compared to their heteroatom bridged analogs.

Keywords

HCV; Hepatitis; NS5B; Propellane; Site I.

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