Selective PPARgamma modulators with improved pharmacological profiles.
A series of metabolically robust N-benzyl-indole selective PPARgamma modulators with either a 3-benzoyl or 3-benzisoxazoyl moiety have been identified. In vitro, these compounds are partial agonists and exhibit reduced adipogenesis in human adipocytes. In vivo, these SPPARgammaMs result in potent glucose lowering in db/db mice and attenuate increases in heart weight and brown adipose tissue that is typically observed in rats upon treatment with PPARgamma full agonists.
Liu
Kun
K
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.
Black
Regina M
RM
Acton
John J
JJ
Mosley
Ralph
R
Debenham
Sheryl
S
Abola
Ramon
R
Yang
Meng
M
Tschirret-Guth
Richard
R
Colwell
Lawrence
L
Liu
Cherrie
C
Wu
Margaret
M
Wang
Chuanlin F
CF
MacNaul
Karen L
KL
McCann
Margaret E
ME
Moller
David E
DE
Berger
Joel P
JP
Meinke
Peter T
PT
Jones
A Brian
AB
Wood
Harold B
HB
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000187:drug effects*; D051381:Rats
D001786:Blood Glucose; D007211:Indoles; D047495:PPAR gamma