Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARalpha/gamma dual agonists.
Aryl-tetrahydropyridine derivatives were prepared and their PPARalpha/gamma dual agonistic activities were evaluated. Among them, compound (S)-5b was identified as a potent PPARalpha/gamma dual agonist with an EC(50) of 1.73 and 0.64 microM in hPPARalpha and gamma, respectively. In diabetic (db/db) mice, compound (S)-5b showed good glucose lowering efficacy and favorable pharmacokinetic properties.
Kim
Eunkyung
E
Yuhan Research Institute, Drug Discovery Laboratory, 416-1, Gongse-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-902, Republic of Korea.
Park
Chan Sun
CS
Han
Taedong
T
Bae
Myung-Ho
MH
Chong
Wonee
W
Lee
Choong Hyun
CH
Shin
Young Ah
YA
Ahn
Byung-Nak
BN
Kim
Mi Kyung
MK
Shin
Chang Yell
CY
Son
Moon Ho
MH
Kim
Jin Kwan
JK
Moon
Ho Sang
HS
Shim
Hyun Joo
HJ
Kim
Eun Jung
EJ
Kim
Soon Hoe
SH
Lim
Joong In
JI
Lee
Chun Ho
CH
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D015195:Drug Design; D051379:Mice; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D047493:PPAR alpha; D047495:PPAR gamma; D011725:Pyridines