title: Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists.
abstract: The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPARα antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARα activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression.
authors: Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
authors: Alessandra
authors: A
authors: Ammazzalorso
authors: Antonella
authors: A
authors: Giancristofaro
authors: Alessandra
authors: A
authors: D'Angelo
authors: Barbara De
authors: BD
authors: Filippis
authors: Marialuigia
authors: M
authors: Fantacuzzi
authors: Letizia
authors: L
authors: Giampietro
authors: Cristina
authors: C
authors: Maccallini
authors: Rosa
authors: R
authors: Amoroso
mesh_terms: D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D010671:Phenylurea Compounds / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D002087:Butyrates; C453899:GW 7647; D047493:PPAR alpha; D010671:Phenylurea Compounds; D013449:Sulfonamides; D002334:Carnitine O-Palmitoyltransferase; C005465:benzothiazole