Abstract:

Objective To synthesize a series of tropane derivatives, and investigate their antagonistic activity and tissue selectivity (trachea/heart) to trachea of rats. Methods A series of 3α-acyloxy-6β-acetoxy tropanes were prepared by acetylating 3α-hydroxy-6β-acetoxy tropane (A0). The antagonistic activities of compounds to muscarinic M2 and M3 receptors on isolated heart and trachea of rats were tested by functional assays respectively. Results Eight tropane compounds were prepared. A1-A4 elicited obvious antagonistic activity to heart and trachea, while A5-A8 had no muscarinic antagonistic activity to heart and trachea. A1 had the highest antagonistic parameter (pA2=7.32) to trachea and higher tissue selectivity (trachea/heart)(ΔpA2=1.51).  Conclusion The antagonistic activity and tissue selectivity (trachea/heart) of compounds to trachea of rats may be improved by decreasing the volume of substituting group connected with phenyl in C-3α position of tropane skeleton or increasing the π-electron density of phenyl ring.

Key words: tropane, muscarinic M3 receptor antagonist, isolated trachea, selectivity