Abstract:

Objective To design and synthesize a series of tropane derivatives, test their antagonistic activity to M3 receptors, and investigate the structure-activity relationship. Methods 3α-benzoyloxy tropanes (D type) and 3α-benzoyloxy-6β-acetoxy tropanes (T type) were prepared by acetylating 3α-hydroxy-tropane (D0) or 3α-hydroxy-6β-acetoxy tropane (T0) respectively. Quaternary ammonium iodide of N-methyl-3α-benzoyloxy tropane (S type) was acquired by methylating the N atom of azabicyclic ring of D type of compounds with methyl iodide. The antagonistic activity of compounds to M3 receptors on isolated tracheal smooth muscles was evaluated by functional assays. Results Six new tropane compounds were prepared, and obvious antagonistic activity to M3 receptors was elicited. S1 had the highest antagonistic parameter (pA2), while T2 had the lowest one. Conclusion Changing the N atom of azabicyclic ring to quaternary from tertiary through methylation increases the antagonistic activity, while the 6β-acetoxy decreases the activity of compounds.

Key words: tropane, M3 receptor antagonist, acetylation, isolated trachea