title: Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors.
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.
authors.affiliation: Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Pfefferkorn
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Song
authors.forename: Kuai-Lin
authors.initials: KL
authors.lastname: Sun
authors.forename: Steven R
authors.initials: SR
authors.lastname: Miller
authors.forename: Bharat K
authors.initials: BK
authors.lastname: Trivedi
authors.forename: Chulho
authors.initials: C
authors.lastname: Choi
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Sorenson
authors.forename: Larry D
authors.initials: LD
authors.lastname: Bratton
authors.forename: Paul C
authors.initials: PC
authors.lastname: Unangst
authors.forename: Scott D
authors.initials: SD
authors.lastname: Larsen
authors.forename: Toni-Jo
authors.initials: TJ
authors.lastname: Poel
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Cheng
authors.forename: Chitase
authors.initials: C
authors.lastname: Lee
authors.forename: Noe
authors.initials: N
authors.lastname: Erasga
authors.forename: Bruce
authors.initials: B
authors.lastname: Auerbach
authors.forename: Valerie
authors.initials: V
authors.lastname: Askew
authors.forename: Lisa
authors.initials: L
authors.lastname: Dillon
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hanselman
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Lin
authors.forename: Gina
authors.initials: G
authors.lastname: Lu
authors.forename: Andrew
authors.initials: A
authors.lastname: Robertson
authors.forename: Karl
authors.initials: K
authors.lastname: Olsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Mertz
authors.forename: Catherine
authors.initials: C
authors.lastname: Sekerke
authors.forename: Alexander
authors.initials: A
authors.lastname: Pavlovsky
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Harris
authors.forename: Graeme
authors.initials: G
authors.lastname: Bainbridge
authors.forename: Nicole
authors.initials: N
authors.lastname: Caspers
authors.forename: Huifen
authors.initials: H
authors.lastname: Chen
authors.forename: Matthias
authors.initials: M
authors.lastname: Eberstadt
mesh_terms: D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy; D008099:Liver / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013329:Structure-Activity Relationship; D013449:Sulfonamides
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium