Design and synthesis of 2-methyl-2-[4-(2-[5-methyl-2-aryloxazol-4-yl]ethoxy)phenoxy]propionic acids: a new class of dual PPARalpha/gamma agonists.
Propionic acid derivative 8, which was designed and synthesized based on putative pharmacophores of known PPARgamma- and PPARalpha-selective compounds, exhibits potent dual PPARalpha/gamma agonist activity as demonstrated by in vitro binding and dose overlap in the newly introduced EOB mouse model for glucose lowering and lipid/cholesterol homeostasis.
Brooks
D A
DA
Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. Brooks_Dawn_A@Lilly.com
Etgen
G J
GJ
Rito
C J
CJ
Shuker
A J
AJ
Dominianni
S J
SJ
Warshawsky
A M
AM
Ardecky
R
R
Paterniti
J R
JR
Tyhonas
J
J
Karanewsky
D S
DS
Kauffman
R F
RF
Broderick
C L
CL
Oldham
B A
BA
Montrose-Rafizadeh
C
C
Winneroski
L L
LL
Faul
M M
MM
McCarthy
J R
JR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011422:Propionates / Q000138:chemical synthesis* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics; D014157:Transcription Factors / Q000819:agonists* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D011422:Propionates; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides