Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds

Vincent Sandanayaka; Bjorn Mamat; Nikhil Bhagat; Louis Bedell; Gudrun Halldorsdottir; Heida Sigthorsdottir; Thorkell Andrésson; Alex Kiselyov; Mark Gurney; Jasbir Singh

doi:10.1016/j.bmcl.2010.03.047

Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds

Bioorg Med Chem Lett. 2010 May 1;20(9):2851-4. doi: 10.1016/j.bmcl.2010.03.047. Epub 2010 Mar 12.

Authors

Vincent Sandanayaka¹, Bjorn Mamat, Nikhil Bhagat, Louis Bedell, Gudrun Halldorsdottir, Heida Sigthorsdottir, Thorkell Andrésson, Alex Kiselyov, Mark Gurney, Jasbir Singh

Affiliation

¹ Medicinal Chemistry Department, deCODE Chemistry, Inc. 2501 Davey Road, Woodridge, IL 60517, United States.

PMID: 20371179
DOI: 10.1016/j.bmcl.2010.03.047

Abstract

Novel piperidine and piperazine derivatives have been designed and tested as inhibitors of LTA(4) hydrolase (LTA(4)H). Most potent compounds showed good potency in both enzymatic and functional human whole blood assay. Crystallography studies further confirmed observed structure-activity relationship and LTA(4)H binding mode for analogs from the piperidine series.

2010. Published by Elsevier Ltd.

MeSH terms

Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology
Binding Sites
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Epoxide Hydrolases / antagonists & inhibitors*
Epoxide Hydrolases / metabolism
Humans
Piperazine
Piperazines / chemical synthesis
Piperazines / chemistry*
Piperazines / pharmacology
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Enzyme Inhibitors
Piperazines
Piperidines
Piperazine
piperidine
Epoxide Hydrolases
leukotriene A4 hydrolase