Development of pharmacophores for inhibitors of the rapid component of the cardiac delayed rectifier potassium current

✍ Scribed by Péter Mátyus; András P. Borosy; András Varró; Julius G. Papp; Daniela Barlocco; Giorgio Cignarella

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 343 KB
• Volume: 69
• Category: Article
• ISSN: 0020-7608
• DOI: 10.1002/(sici)1097-461x(1998)69:1<21::aid-qua4>3.0.co;2-z

✦ Synopsis

Blockade of cardiac-delayed rectifier potassium current I is an Kr important mechanism for Class III antiarrhythmic effect. We developed pharmacophores for I inhibitors starting from structures of known blockers. To obtain the Kr pharmacophores, DISCO module of SYBYL was used. Conformations required for DISCO computations were provided by Multisearch type conformational analyses. A common five-point three-dimensional relationship was identified for the most active compounds, whereas a four-point pharmacophore forming a subset of the former one, could be developed for less potent agents.