639091-30-8Relevant articles and documents
Synthesis and structure-activity relationships of phenoxypyridine derivatives as novel inhibitors of the sodium-calcium exchanger
Kuramochi, Takahiro,Kakefuda, Akio,Yamada, Hiroyoshi,Sato, Ippei,Taguchi, Taku,Sakamoto, Shuichi
, p. 5039 - 5056 (2004)
A series of 2-phenoxypyridine derivatives were prepared and evaluated for their inhibitory activity against the reverse and forward modes of the sodium-calcium exchanger (NCX). The structure-activity relationships of these compounds on the inhibitory activity for the sodium-calcium exchanger are discussed. The sodium-calcium exchanger (NCX) is known as the transporter that controls the concentration of Ca2+ in cardiac myocytes. In the setting of heart failure and myocardial ischemia-reperfusion, NCX underlies an arrhythmogenic transient inward current responsible for delayed after-depolarizations and nonreentrant initiation of ventricular tachycardia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of phenoxypyridine derivatives, based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward mode of NCX in CCL39 cells. We have discovered several novel potent NCX inhibitors (39q, 48k), which have a high selectivity for reverse NCX inhibitory activity.
