Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents
| Autor: | Irving Fong, Elfatih Elzein, Prabha Ibrahim, Lin Wu, Jeff Zablocki, Timothy A. Marquart, Yuzhi Wu, David Lustig, Dewan Zeng, Christopher Morrison, Tenning Maa, Bob Jiang, Kevin D. Shenk, Kwan Leung, Venkata Palle, Vaibhav Varkhedkar |
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| Rok vydání: | 2004 |
| Předmět: |
Bundle of His
medicine.medical_specialty Adenosine medicine.medical_treatment Guinea Pigs Clinical Biochemistry GTPgammaS Pharmaceutical Science Sulfides Antiarrhythmic agent Hydrocarbons Aromatic Biochemistry Partial agonist Structure-Activity Relationship chemistry.chemical_compound Adenosine A1 receptor Heart Rate Internal medicine Drug Discovery medicine Animals Receptor Molecular Biology Binding Sites Dose-Response Relationship Drug Receptor Adenosine A1 Organic Chemistry Arrhythmias Cardiac Adenosine receptor Adenosine A1 Receptor Agonists Endocrinology chemistry Dromotropic Atrioventricular Node Molecular Medicine Anti-Arrhythmia Agents Ethers medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 14:3793-3797 |
| ISSN: | 0960-894X |
| Popis: | Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A(1) adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A(1) adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A(1) adenosine receptor could avoid this deleterious effect. 5(') Phenyl sulfides (e.g., 17, EC(50)=1.26 microM) and phenyl ethers (e.g., 28, EC(50)=0.2 microM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5(') modified adenosine derivatives are shown. |
| Databáze: | OpenAIRE |
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