title: Indanylacetic acid derivatives carrying aryl-pyridyl and aryl-pyrimidinyl tail groups--new classes of PPAR gamma/delta and PPAR alpha/gamma/delta agonists.
abstract: Modulation of PPAR activities represents an attractive approach for the treatment of diabetes with associated cardiovascular complications. The indanylacetic acid structural motif has proven useful in the generation of potent and tunable PPAR ligands. Modification of the substituents on the linker and the heterocycle tail group allowed for the modulation of the selectivity at the different receptor subtypes. Compound 33 was evaluated in vivo, where it displayed the desired reduction of glucose levels and increase in HDL levels in various animal models.
authors.affiliation: Department of Chemistry Research, Bayer Pharmaceuticals Corporation, West Haven, CT 06516, USA. david.cantin.b@bayer.com
authors.forename: Louis-David
authors.initials: LD
authors.lastname: Cantin
authors.forename: Sidney
authors.initials: S
authors.lastname: Liang
authors.forename: Herbert
authors.initials: H
authors.lastname: Ogutu
authors.forename: Christiana I
authors.initials: CI
authors.lastname: Iwuagwu
authors.forename: Ken
authors.initials: K
authors.lastname: Boakye
authors.forename: William H
authors.initials: WH
authors.lastname: Bullock
authors.forename: Michael
authors.initials: M
authors.lastname: Burns
authors.forename: Roger
authors.initials: R
authors.lastname: Clark
authors.forename: Thomas
authors.initials: T
authors.lastname: Claus
authors.forename: Fernando E
authors.initials: FE
authors.lastname: delaCruz
authors.forename: Michelle
authors.initials: M
authors.lastname: Daly
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Ehrgott
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Johnson
authors.forename: Christine
authors.initials: C
authors.lastname: Keiper
authors.forename: James N
authors.initials: JN
authors.lastname: Livingston
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schoenleber
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shapiro
authors.forename: Christopher
authors.initials: C
authors.lastname: Town
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Manami
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008075:Lipoproteins, HDL / Q000097:blood; D051379:Mice; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D000085:Acetates; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007189:Indans; D007202:Indicators and Reagents; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002784:Cholesterol