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

Péter Mátyus, András P. Borosy, András Varro, Julius G. Papp, Daniela Barlocco, Giorgio Cignarella

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27 Citations (Scopus)

Abstract

Blockade of cardiac-delayed rectifier potassium current (IKr) is an important mechanism for Class III antiarrhythmic effect. We developed pharmacophores for IKr inhibitors starting from structures of known blockers. To obtain the 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.

Original languageEnglish
Pages (from-to)21-30
Number of pages10
JournalInternational Journal of Quantum Chemistry
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 1 1998

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Keywords

  • Antiarrhythmic agents
  • Conformational analysis
  • DISCO
  • Dofetilide
  • Pharmacophore

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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