Design and synthesis of a novel class of dual PPARgamma/delta agonists.
The design and synthesis of dual PPAR gamma/delta agonist (R)-3-{2-ethyl-4-[3-(4-ethyl-2-pyridin-2-yl-phenoxy)-butoxy]-phenyl}propionic acid is described. This compound dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats and produced less weight gain relative to rosiglitazone at an equivalent level of glucose control.
Gonzalez
Isabel C
IC
Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate center, Indianapolis, IN 46285, USA. gonzalez_isabel_c@lilly.com
Lamar
Jason
J
Iradier
Fatima
F
Xu
Yanping
Y
Winneroski
Leonard L
LL
York
Jeremy
J
Yumibe
Nathan
N
Zink
Richard
R
Montrose-Rafizadeh
Chahrzad
C
Etgen
Gary J
GJ
Broderick
Carol L
CL
Oldham
Brian A
BA
Mantlo
Nathan
N
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007202:Indicators and Reagents; D007328:Insulin / Q000097:blood; D008297:Male; D047494:PPAR delta / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D007328:Insulin; D047494:PPAR delta; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone