Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties

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.