title: Selective PPARgamma modulators with improved pharmacological profiles.
abstract: A series of metabolically robust N-benzyl-indole selective PPARgamma modulators with either a 3-benzoyl or 3-benzisoxazoyl moiety have been identified. In vitro, these compounds are partial agonists and exhibit reduced adipogenesis in human adipocytes. In vivo, these SPPARgammaMs result in potent glucose lowering in db/db mice and attenuate increases in heart weight and brown adipose tissue that is typically observed in rats upon treatment with PPARgamma full agonists.
authors.affiliation: Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Regina M
authors.initials: RM
authors.lastname: Black
authors.forename: John J
authors.initials: JJ
authors.lastname: Acton
authors.forename: Ralph
authors.initials: R
authors.lastname: Mosley
authors.forename: Sheryl
authors.initials: S
authors.lastname: Debenham
authors.forename: Ramon
authors.initials: R
authors.lastname: Abola
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Tschirret-Guth
authors.forename: Lawrence
authors.initials: L
authors.lastname: Colwell
authors.forename: Cherrie
authors.initials: C
authors.lastname: Liu
authors.forename: Margaret
authors.initials: M
authors.lastname: Wu
authors.forename: Chuanlin F
authors.initials: CF
authors.lastname: Wang
authors.forename: Karen L
authors.initials: KL
authors.lastname: MacNaul
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McCann
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
authors.forename: A Brian
authors.initials: AB
authors.lastname: Jones
authors.forename: Harold B
authors.initials: HB
authors.lastname: Wood
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000187:drug effects*; D051381:Rats
chemical_list: D001786:Blood Glucose; D007211:Indoles; D047495:PPAR gamma