Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4.
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.
Blackburn
Christopher
C
Medicinal Chemistry, Millennium Pharmaceuticals, Inc., 40 Landsdowne St., Cambridge, MA 02139, USA. chris.blackburn@mpi.com
Guan
Bing
B
Brown
James
J
Cullis
Courtney
C
Condon
Stephen M
SM
Jenkins
Tracy J
TJ
Peluso
Stephane
S
Ye
Yingchun
Y
Gimeno
Ruth E
RE
Punreddy
Sandhya
S
Sun
Ying
Y
Wu
Hui
H
Hubbard
Brian
B
Kaushik
Virendar
V
Tummino
Peter
P
Sanchetti
Praveen
P
Yu Sun
Dong
D
Daniels
Tom
T
Tozzo
Effie
E
Balani
Suresh K
SK
Raman
Prakash
P
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
D050612:Fatty Acid Transport Proteins; D011744:Pyrimidinones; C493571:SLC27A4 protein, human