title: 3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists: Part 1.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, The Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA. repple@gnf.org
authors.forename: Robert
authors.initials: R
authors.lastname: Epple
authors.forename: Ross
authors.initials: R
authors.lastname: Russo
authors.forename: Mihai
authors.initials: M
authors.lastname: Azimioara
authors.forename: Christopher
authors.initials: C
authors.lastname: Cow
authors.forename: Yongping
authors.initials: Y
authors.lastname: Xie
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Wityak
authors.forename: Don
authors.initials: D
authors.lastname: Karanewsky
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerken
authors.forename: Maya
authors.initials: M
authors.lastname: Iskandar
authors.forename: Enrique
authors.initials: E
authors.lastname: Saez
authors.forename: H
authors.initials: H
authors.lastname: Martin Seidel
authors.forename: Shin-Shay
authors.initials: SS
authors.lastname: Tian
mesh_terms: 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
chemical_list: D007555:Isoxazoles; D047494:PPAR delta; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors