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

Tetsuyoshi Matsufuji; Mika Ikeda; Asuka Naito; Masakazu Hirouchi; Shoichi Kanda; Masanori Izumi; Jun Harada; Tsuyoshi Shinozuka

doi:10.1016/j.bmcl.2013.02.116

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

Bioorg Med Chem Lett. 2013 May 1;23(9):2560-5. doi: 10.1016/j.bmcl.2013.02.116. Epub 2013 Mar 7.

Authors

Tetsuyoshi Matsufuji¹, Mika Ikeda, Asuka Naito, Masakazu Hirouchi, Shoichi Kanda, Masanori Izumi, Jun Harada, Tsuyoshi Shinozuka

Affiliation

¹ Lead Discovery & Optimization Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Tokyo 140-8710, Japan.

PMID: 23528296
DOI: 10.1016/j.bmcl.2013.02.116

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.

MeSH terms

Animals
Fatty Acid Transport Proteins / antagonists & inhibitors*
Fatty Acid Transport Proteins / metabolism
Half-Life
Humans
Liver / metabolism
Mice
Muscle, Skeletal / metabolism
Piperazines / chemical synthesis
Piperazines / chemistry*
Piperazines / pharmacokinetics
Protein Binding
Structure-Activity Relationship
Triglycerides / metabolism

Substances

Fatty Acid Transport Proteins
Piperazines
SLC27A1 protein, human
Slc27a1 protein, mouse
Triglycerides