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1: Bioorg Med Chem Lett. 2007 Aug 15;17(16):4538-44. Epub 2007 Jun 6.
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Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors.

Pfefferkorn JA, Song Y, Sun KL, Miller SR, Trivedi BK, Choi C, Sorenson RJ, Bratton LD, Unangst PC, Larsen SD, Poel TJ, Cheng XM, Lee C, Erasga N, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu G, Robertson A, Olsen K, Mertz T, Sekerke C, Pavlovsky A, Harris MS, Bainbridge G, Caspers N, Chen H, Eberstadt M.

Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com

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.

PMID: 17574412 [PubMed - indexed for MEDLINE]