Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase

John M Keith; Richard Apodaca; Wei Xiao; Mark Seierstad; Kanaka Pattabiraman; Jiejun Wu; Michael Webb; Mark J Karbarz; Sean Brown; Sandy Wilson; Brian Scott; Chui-Se Tham; Lin Luo; James Palmer; Michelle Wennerholm; Sandra Chaplan; J Guy Breitenbucher

doi:10.1016/j.bmcl.2008.07.081

Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4838-43. doi: 10.1016/j.bmcl.2008.07.081. Epub 2008 Jul 25.

Authors

John M Keith¹, Richard Apodaca, Wei Xiao, Mark Seierstad, Kanaka Pattabiraman, Jiejun Wu, Michael Webb, Mark J Karbarz, Sean Brown, Sandy Wilson, Brian Scott, Chui-Se Tham, Lin Luo, James Palmer, Michelle Wennerholm, Sandra Chaplan, J Guy Breitenbucher

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA.

PMID: 18693015
DOI: 10.1016/j.bmcl.2008.07.081

Abstract

A series of thiadiazolopiperazinyl aryl urea fatty acid amide hydrolase (FAAH) inhibitors is described. The molecules were found to inhibit the enzyme by acting as mechanism-based substrates, forming a covalent bond with Ser241. SAR and PK properties are presented.

Publication types

Comparative Study

MeSH terms

Amidohydrolases / antagonists & inhibitors*
Amidohydrolases / deficiency
Amidohydrolases / genetics
Animals
Mice
Mice, Knockout
Piperazines / chemistry
Piperazines / pharmacokinetics
Piperazines / pharmacology*
Thiadiazoles / chemistry
Thiadiazoles / pharmacokinetics
Thiadiazoles / pharmacology*
Urea / analogs & derivatives*
Urea / chemistry
Urea / pharmacokinetics
Urea / pharmacology*

Substances

Piperazines
Thiadiazoles
Urea
Amidohydrolases
fatty-acid amide hydrolase