Abstract: Objective · To provide theoretical guidance for the design of molecules with high activitybuilding the quantitative structure-activity relationship (QSAR) model for tropane compounds as muscarinic M3 receptor antagonists. Methods · Six compounds (J1-J6) were prepared with 3α-hydroxy-tropane (J0) as the starting materialmodifying the structure in C-3α position of the tropane skeleton. The antagonistic activity of new tropane compounds to muscarinic M3 receptors on tracheal rings of guinea pigs was evaluatedfunctional assays in vitro. The antagonistic parameters (pA2) of new tropane compounds prepared in this paper and former studies were applied to construct the QSAR model. The information about structural optimization was acquiredanalyzing the effect of steric field and electrostatic field of model on activity of tropane compounds. Results · The six new tropane compounds showed obvious antagonistic activity against M3 receptors. Among them, J4 had the greatest activity (pA27.992). The cross-validation correlation coefficient squared (q2) and the non-cross-validated correlation coefficient squared (r2) of the QSAR model were 0.585 and 0.993, respectively. Conclusion · The antagonistic activity to muscarinic M3 receptors can be obviously improved, when the conjugating extent of π-bonds is large and O or N atoms participate in conjugation on the rings in the R-substituting group at C-3α position of the compounds. [Key words]chronic obstructive pulmonary disease (COPD); tropane; M3 receptor antagonist; quantitative structure-activity relationship (QSAR)

Key words: chronic obstructive pulmonary disease (COPD), tropane, M3 receptor antagonist, quantitative structure-activity relationship (QSAR)