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Development of pharmacophores for inhibitors of the rapid component of the cardiac delayed rectifier potassium current
Author(s) -
Mátyus Péter,
Borosy András P.,
Varró András,
Papp Julius G.,
Barlocco Daniela,
Cignarella Giorgio
Publication year - 1998
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1998)69:1<21::aid-qua4>3.0.co;2-z
Subject(s) - pharmacophore , chemistry , blockade , combinatorial chemistry , stereochemistry , biochemistry , receptor
Blockade of cardiac‐delayed rectifier potassium current ( I Kr ) is an important mechanism for Class III antiarrhythmic effect. We developed pharmacophores for I Kr 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. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 21–30, 1998