title: Discovery of N-(3-{4-[(3-fluorobenzyl)oxy]phenoxy}propyl)-2-pyridin-4-ylacetamide as a potent and selective reverse NCX inhibitor.
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.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. takahiro.kuramochi@jp.astellas.com
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuramochi
authors.forename: Akio
authors.initials: A
authors.lastname: Kakefuda
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogiyama
authors.forename: Taku
authors.initials: T
authors.lastname: Taguchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000737:chemistry*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000081:Acetamides; C504504:N-(3-(4-((3-fluorobenzyl)oxy)phenoxy)propyl)-2-pyridin-4-ylacetamide; D011725:Pyridines; D019831:Sodium-Calcium Exchanger