Acta Phys. -Chim. Sin. ›› 2004, Vol. 20 ›› Issue (05): 488-493.doi: 10.3866/PKU.WHXB20040509

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3D-QSAR Study of Benzodiazepines at Five Recombinant GABAA/Benzodiazepine Receptor Subtypes

Lu Ai-Jun;Liu Bing;Liu Hai-Bo;Zhou Jia-Ju   

  1. Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080
  • Received:2003-11-14 Revised:2003-12-21 Published:2004-05-15
  • Contact: Zhou Jia-Ju

Abstract: GABAA receptor is the major neurotransmitter system in the central nervous system(CNS) and elicits a wide range of neuronal physiological activities. Since anxiolytic/anticonvulsant agents have been employed widely in clinic, the receptor sites for the benzodiazepine are of prime importance. Studies on quantitative structure-activity relationship with CoMFA for the binding affinities of a series of imidazobenzodiazepines at five recombinant receptor subtypes were carried out successfully, and a good crossvalidated correlation was obtained for each receptor subtype. Then a set of non-cross-validated PLS models was built and permitted demonstration of high predictability for the affinities of the six ligands in the test set selected in random at all five receptor subtypes. The modals can help design high affinitiy ligands on the GABAA/BZ receptor and understand the GABAA receptor modal.

Key words: Comparative mo1ecular field analysis(CoMFA), Benzodiazepine(BZ),  GABAA receptor