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
  • 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.