title: Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties.
abstract: The discovery and optimization of a novel series of FATP1 inhibitors are described. Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties. In vivo evaluation of triglyceride accumulation in the liver, white gastrocnemius muscle and soleus is also described.
authors.affiliation: Lead Discovery & Optimization Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Tokyo 140-8710, Japan.
authors.forename: Tetsuyoshi
authors.initials: T
authors.lastname: Matsufuji
authors.forename: Mika
authors.initials: M
authors.lastname: Ikeda
authors.forename: Asuka
authors.initials: A
authors.lastname: Naito
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hirouchi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kanda
authors.forename: Masanori
authors.initials: M
authors.lastname: Izumi
authors.forename: Jun
authors.initials: J
authors.lastname: Harada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shinozuka
mesh_terms: D000818:Animals; D050612:Fatty Acid Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism
chemical_list: D050612:Fatty Acid Transport Proteins; D010879:Piperazines; C493568:SLC27A1 protein, human; C493569:Slc27a1 protein, mouse; D014280:Triglycerides