Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands.
PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes.
Warshawsky
Alan M
AM
Eli Lilly and Co, Indianapolis, IN 46285, USA. amw@lilly.com
Alt
Charles A
CA
Brozinick
Joseph T
JT
Harkness
Allen R
AR
Hawkins
Eric D
ED
Henry
James R
JR
Matthews
Donald P
DP
Miller
Anne R
AR
Misener
Elizabeth A
EA
Montrose-Rafizadeh
Chahrzad
C
Rhodes
Gary A
GA
Shen
Quanrong
Q
Vance
Jennifer A
JA
Udodong
Uko E
UE
Wang
Minmin
M
Zhang
Tony Y
TY
Zink
Richard W
RW
D002934:Cinnamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008024:Ligands; D047493:PPAR alpha / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology*; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000627:therapeutic use
D002934:Cinnamates; D007004:Hypoglycemic Agents; D008024:Ligands; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones