title: Benzoyl 2-methyl indoles as selective PPARgamma modulators.
abstract: Routine screening for human PPAR ligands yielded compounds 1 and 2, both of which were sub-micromolar hPPARgamma agonists. Synthetic modifications of these leads led to a series of potent substituted 3-benzyl-2-methyl indoles, a subset of which were noted to be selective PPARgamma modulators (SPPARgammaMs). SPPARgammaM 24 displayed robust anti-diabetic activity with an improved therapeutic window in comparison to a PPARgamma full agonist in a rodent efficacy model.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. john_acton@merck.com
authors.forename: John J
authors.initials: JJ
authors.lastname: Acton
authors.forename: Regina M
authors.initials: RM
authors.lastname: Black
authors.forename: A Brian
authors.initials: AB
authors.lastname: Jones
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
authors.forename: Lawrence
authors.initials: L
authors.lastname: Colwell
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Doebber
authors.forename: Karen L
authors.initials: KL
authors.lastname: Macnaul
authors.forename: Joel
authors.initials: J
authors.lastname: Berger
authors.forename: Harold B
authors.initials: HB
authors.lastname: Wood
mesh_terms: D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism
chemical_list: D001565:Benzoates; D007211:Indoles; D018836:Inflammation Mediators; D008024:Ligands; D047495:PPAR gamma