Discovery of N-(3-{4-[(3-fluorobenzyl)oxy]phenoxy}propyl)-2-pyridin-4-ylacetamide as a potent and selective reverse NCX inhibitor |
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Authors: | Kuramochi Takahiro Kakefuda Akio Yamada Hiroyoshi Ogiyama Takashi Taguchi Taku Sakamoto Shuichi |
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Institution: | Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. takahiro.kuramochi@jp.astellas.com |
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Abstract: | In the setting of heart failure and myocardial ischemia-reperfusion, the sodium-calcium exchanger (NCX) can lead to calcium overload, which is responsible for contractile dysfunction and arrhythmia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of benzyloxyphenyl derivatives based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward modes of NCX. We have discovered a novel potent and selective reverse NCX inhibitor (12) with an IC50 value of 0.085 microM against reverse NCX. |
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