2. Academic Validation
  3. Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

  • Bioorg Med Chem Lett. 2007 Aug 15;17(16):4538-44. doi: 10.1016/j.bmcl.2007.05.096.
Jeffrey A Pfefferkorn 1,  Yuntao Song,  Kuai-Lin Sun,  Steven R Miller,  Bharat K Trivedi,  Chulho Choi,  Roderick J Sorenson,  Larry D Bratton,  Paul C Unangst,  Scott D Larsen,  Toni-Jo Poel,  Xue-Min Cheng,  Chitase Lee,  Noe Erasga,  Bruce Auerbach,  Valerie Askew,  Lisa Dillon,  Jeffrey C Hanselman,  Zhiwu Lin,  Gina Lu,  Andrew Robertson,  Karl Olsen,  Thomas Mertz,  Catherine Sekerke,  Alexander Pavlovsky,  Melissa S Harris,  Graeme Bainbridge,  Nicole Caspers,  Huifen Chen,  Matthias Eberstadt
Affiliations

Affiliation

  • 1 Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. [email protected]
PMID: 17574412 DOI: 10.1016/j.bmcl.2007.05.096
Abstract

This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

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