title: Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4.
abstract: Several potent, cell permeable 4-aryl-dihydropyrimidinones have been identified as inhibitors of FATP4. Lipophilic ester substituents at the 5-position and substitution at the para-position (optimal groups being -NO(2) and CF(3)) of the 4-aryl group led to active compounds. In two cases racemates were resolved and the S enantiomers shown to have higher potencies.
authors.affiliation: Medicinal Chemistry, Millennium Pharmaceuticals, Inc., 40 Landsdowne St., Cambridge, MA 02139, USA. chris.blackburn@mpi.com
authors.forename: Christopher
authors.initials: C
authors.lastname: Blackburn
authors.forename: Bing
authors.initials: B
authors.lastname: Guan
authors.forename: James
authors.initials: J
authors.lastname: Brown
authors.forename: Courtney
authors.initials: C
authors.lastname: Cullis
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Condon
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Jenkins
authors.forename: Stephane
authors.initials: S
authors.lastname: Peluso
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Ye
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Gimeno
authors.forename: Sandhya
authors.initials: S
authors.lastname: Punreddy
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Brian
authors.initials: B
authors.lastname: Hubbard
authors.forename: Virendar
authors.initials: V
authors.lastname: Kaushik
authors.forename: Peter
authors.initials: P
authors.lastname: Tummino
authors.forename: Praveen
authors.initials: P
authors.lastname: Sanchetti
authors.forename: Dong
authors.initials: D
authors.lastname: Yu Sun
authors.forename: Tom
authors.initials: T
authors.lastname: Daniels
authors.forename: Effie
authors.initials: E
authors.lastname: Tozzo
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Balani
authors.forename: Prakash
authors.initials: P
authors.lastname: Raman
mesh_terms: D002460:Cell Line; D050612:Fatty Acid Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D050612:Fatty Acid Transport Proteins; D011744:Pyrimidinones; C493571:SLC27A4 protein, human