Discovery and optimization of novel fatty acid transport protein 1 (FATP1) inhibitors

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

doi:10.1016/j.bmcl.2012.05.130

Discovery and optimization of novel fatty acid transport protein 1 (FATP1) inhibitors

Bioorg Med Chem Lett. 2012 Aug 1;22(15):5067-70. doi: 10.1016/j.bmcl.2012.05.130. Epub 2012 Jun 19.

Authors

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

Affiliation

¹ Lead Discovery & Optimization Research Laboratories I, Daiichi Sankyo Co., Ltd, Shinagawa-ku, Tokyo, Japan.

PMID: 22749869
DOI: 10.1016/j.bmcl.2012.05.130

Abstract

The discovery, optimization and structure-activity relationship of novel FATP1 inhibitors have been described. The detailed SAR studies of each moiety of the inhibitors combined with metabolite analysis led to the identification of the potent inhibitors 11p and 11q with improved blood stability.

MeSH terms

Administration, Oral
Animals
Benzoxazoles / chemical synthesis
Benzoxazoles / chemistry*
Benzoxazoles / pharmacokinetics
Drug Evaluation, Preclinical
Fatty Acid Transport Proteins / antagonists & inhibitors*
Fatty Acid Transport Proteins / metabolism
Humans
Injections, Intravenous
Mice
Rats
Structure-Activity Relationship
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacokinetics

Substances

Benzoxazoles
Fatty Acid Transport Proteins
N-((4-ethyl-5-(((5-(trifluoromethoxy)-1,3-benzoxazol-2-yl)methyl)sulfanyl)-4H-1,2,4-triazol-3-yl)methyl)aniline
Triazoles