3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists: Part 1.
We report the identification of a novel series of trisubstituted isoxazoles as PPAR activators from a high-throughput screen. A series of structural optimizations led to improved efficacy and excellent functional receptor selectivity for PPARdelta. The isoxazoles represent a series of agonists which display a scaffold that lies outside the typical PPAR agonist motif.
Epple
Robert
R
Department of Medicinal Chemistry, The Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA. repple@gnf.org
Russo
Ross
R
Azimioara
Mihai
M
Cow
Christopher
C
Xie
Yongping
Y
Wang
Xing
X
Wityak
John
J
Karanewsky
Don
D
Gerken
Andrea
A
Iskandar
Maya
M
Saez
Enrique
E
Martin Seidel
H
H
Tian
Shin-Shay
SS
D020816:Amino Acid Motifs; D000818:Animals; D007555:Isoxazoles / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D007555:Isoxazoles; D047494:PPAR delta; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors