title: 2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.
abstract: Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.
authors.affiliation: Lilly Research Laboratories, Division of Eli Lilly & Company, Lilly S.A., Alcobendas 28108, Madrid, Spain. martin_jose_alfredo@lilly.com
authors.forename: José A
authors.initials: JA
authors.lastname: Martín
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Brooks
authors.forename: Lourdes
authors.initials: L
authors.lastname: Prieto
authors.forename: Rosario
authors.initials: R
authors.lastname: González
authors.forename: Alicia
authors.initials: A
authors.lastname: Torrado
authors.forename: Isabel
authors.initials: I
authors.lastname: Rojo
authors.forename: Beatriz
authors.initials: B
authors.lastname: López de Uralde
authors.forename: Carlos
authors.initials: C
authors.lastname: Lamas
authors.forename: Rafael
authors.initials: R
authors.lastname: Ferritto
authors.forename: María
authors.initials: M
authors.lastname: Dolores Martín-Ortega
authors.forename: Javier
authors.initials: J
authors.lastname: Agejas
authors.forename: Francisco
authors.initials: F
authors.lastname: Parra
authors.forename: John R
authors.initials: JR
authors.lastname: Rizzo
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rhodes
authors.forename: Roger L
authors.initials: RL
authors.lastname: Robey
authors.forename: Charles A
authors.initials: CA
authors.lastname: Alt
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Wendel
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Zhang
authors.forename: Anne
authors.initials: A
authors.lastname: Reifel-Miller
authors.forename: Chahrzad
authors.initials: C
authors.lastname: Montrose-Rafizadeh
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Brozinick
authors.forename: Eric
authors.initials: E
authors.lastname: Hawkins
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Misener
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Briere
authors.forename: Robert
authors.initials: R
authors.lastname: Ardecky
authors.forename: James D
authors.initials: JD
authors.lastname: Fraser
authors.forename: Alan M
authors.initials: AM
authors.lastname: Warshawsky
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002934:Cinnamates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D051381:Rats; D011924:Rats, Zucker; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D002934:Cinnamates; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; C029010:cinnamic acid