Amiloride derived inhibitors of acid-sensing ion channel-3 (ASIC3)

Scott D Kuduk; Christina N Di Marco; Ronald K Chang; Robert M Dipardo; Sean P Cook; Matthew J Cato; Aneta Jovanovska; Mark O Urban; Michael Leitl; Robert H Spencer; Stefanie A Kane; Mark T Bilodeau; George D Hartman; Mark G Bock

doi:10.1016/j.bmcl.2009.03.029

Amiloride derived inhibitors of acid-sensing ion channel-3 (ASIC3)

Bioorg Med Chem Lett. 2009 May 1;19(9):2514-8. doi: 10.1016/j.bmcl.2009.03.029. Epub 2009 Mar 14.

Authors

Scott D Kuduk¹, Christina N Di Marco, Ronald K Chang, Robert M Dipardo, Sean P Cook, Matthew J Cato, Aneta Jovanovska, Mark O Urban, Michael Leitl, Robert H Spencer, Stefanie A Kane, Mark T Bilodeau, George D Hartman, Mark G Bock

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.

PMID: 19339181
DOI: 10.1016/j.bmcl.2009.03.029

Abstract

A series of amiloride derivatives modified at the 5-position of the pyrazine ring were evaluated as inhibitors of acid-sensing ion channel-3 (ASIC3), a novel target for the treatment of chronic pain.

MeSH terms

Acid Sensing Ion Channels
Acidosis
Amiloride / analogs & derivatives*
Amiloride / chemistry
Amines / chemistry
Animals
Chemistry, Pharmaceutical / methods*
Drug Design
Electrophysiology
Inhibitory Concentration 50
Male
Models, Chemical
Nerve Tissue Proteins / chemistry*
Pain / drug therapy*
Pyrazines / chemistry
Rats
Rats, Sprague-Dawley
Sodium Channels / chemistry*

Substances

ASIC3 protein, rat
Acid Sensing Ion Channels
Amines
Nerve Tissue Proteins
Pyrazines
Sodium Channels
Amiloride