Synthesis and structure–activity relationships of phenoxypyridine derivatives as novel inhibitors of the sodium–calcium exchanger
| Autor: | Ippei Sato, Shuichi Sakamoto, Taku Taguchi, Akio Kakefuda, Hiroyoshi Yamada, Takahiro Kuramochi |
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| Rok vydání: | 2004 |
| Předmět: |
Pyridines
Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element Pharmacology Calcium Ventricular tachycardia Inhibitory postsynaptic potential Biochemistry Sodium-Calcium Exchanger Cell Line Inhibitory Concentration 50 Necrosis Structure-Activity Relationship Cricetinae Drug Discovery medicine Animals Myocyte Molecular Biology Sodium-calcium exchanger Organic Chemistry Transporter Fibroblasts medicine.disease In vitro chemistry Heart failure Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 12:5039-5056 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2004.07.038 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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