title: Identification of the first potent, selective and bioavailable PPARα antagonist.
abstract: The discovery and SAR of a novel series of potent and selective PPARα antagonists are herein described. Exploration of replacements for the labile acyl sulfonamide linker led to a biaryl sulfonamide series of which compound 33 proved to be suitable for further profiling in vivo. Compound 33 demonstrated excellent potency, selectivity against other nuclear hormone receptors, and good pharmacokinetics in mouse.
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA. Electronic address: yaldabravo47@gmail.com.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Bravo
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Baccei
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Broadhead
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bundey
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Chen
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Clark
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Correa
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Jacintho
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lorrain
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Stebbins
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
authors.affiliation: Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
mesh_terms: D000818:Animals; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002087:Butyrates; C442829:GW 409544; C453899:GW 7647; C479889:LY 518674; D010080:Oxazoles; D047493:PPAR alpha; D010671:Phenylurea Compounds; D011422:Propionates; D013449:Sulfonamides; D014230:Triazoles; D014443:Tyrosine
keywords: Antagonist; Cancer; Fatty acid oxidation; Nuclear hormone receptor; PPAR alpha