2. Academic Validation
  3. Late-Stage Microsomal Oxidation Reduces Drug-Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189

Late-Stage Microsomal Oxidation Reduces Drug-Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189

  • ACS Med Chem Lett. 2018 Jan 4;9(2):68-72. doi: 10.1021/acsmedchemlett.7b00343.
Antonia F Stepan 1,  Tuan P Tran 2,  Christopher J Helal 2,  Maria S Brown 2,  Cheng Chang 2,  Rebecca E O'Connor 2,  Michael De Vivo 1,  Shawn D Doran 2,  Ethan L Fisher 2,  Stephen Jenkinson 3,  David Karanian 2,  Bethany L Kormos 1,  Raman Sharma 2,  Gregory S Walker 2,  Ann S Wright 2,  Edward X Yang 2,  Michael A Brodney 1,  Travis T Wager 1,  Patrick R Verhoest 1,  R Scott Obach 2
Affiliations

Affiliations

  • 1 Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, Massachusetts 02139, United States.
  • 2 Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States.
  • 3 Pfizer Worldwide Research and Development, 10770 Science Center Drive, La Jolla, California 92121, United States.
PMID: 29456790 DOI: 10.1021/acsmedchemlett.7b00343
Abstract

Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor 1 to reduce its clearance by Cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 (2) with improved physicochemical properties and a mixed metabolic profile. This example highlights the importance of C-H diversification methods to drug discovery.

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