title: Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors.
abstract: Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.
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: Chulho
authors.initials: C
authors.lastname: Choi
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Song
authors.forename: Bharat K
authors.initials: BK
authors.lastname: Trivedi
authors.forename: Scott D
authors.initials: SD
authors.lastname: Larsen
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: Catherine
authors.initials: C
authors.lastname: Sekerke
authors.forename: Bruce
authors.initials: B
authors.lastname: Auerbach
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
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D015195:Drug Design; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy; D051379:Mice; D008967:Molecular Biology; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol