THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF GPIIb/IIIa ANTAGONISTS

AIM：To disclose the relationship between activity and structure of a new class of non-peptide fibrinogen receptor antagonists. METHODS AND RESULTS: A series of 16 GPIIb/IIIa antagonists were investigated with the aim of developing a 3D-QSAR model using comparative molecular field analysis(CoMFA). The active conformation and the alignment of the whole molecule were extracted from the sibrafiban crystal structure. The model shows higher ability to explain and predict the activity of GPIIb/IIIa antagonists, and cross-validated R_ev²=0.834, Non cross-validated R²=0.988, F=323.63, SE(standard error of estimate)=0.135. CONCLUSION: The 3D-model is consistent with the experiments.