›› 2011, Vol. 31 ›› Issue (7): 909-.doi: 10.3969/j.issn.1674-8115.2011.07.009

• Original article (Basic research) • Previous Articles     Next Articles

Synthesis of tropane compounds and their antagonistic activity to M3 receptors

OU Mei-xian, SHI Yi-ming, LIU Hui-zhong, CUI Yong-yao, ZHU Liang, NIU Yin-yao, CHEN Hong-zhuan, LU Yang   

  1. Department of Pharmacy, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-07-28 Published:2011-07-27
  • Supported by:

    Shanghai Natural Science Foundation, 10ZR1416900


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