Identification of some novel xanthine-based derivatives with bronchodilator activity

Abstract

Aim: The discovery of new bronchodilators with higher efficacy than theophylline is an important issue for asthmatic patients. Materials & methods: Theophylline 2, 8-bromotheophylline 4 and theobromine 6 were reacted with different 2/3-chloro-N-phenylacetamides 1a-d or their propanamide analogs 1e-g to obtain 3a-g, 5a-g and 7a-g, respectively. The target compounds were screened for their in vitro bronchodilator activity using isolated guinea pig tracheal rings precontracted with histamine and compared with their precursors. Results: Many compounds exhibited promising activity especially 3d, 3f, 5d, 7d and 7e. 2D-QSAR study resulted in a significant model (N = 24, n = 5, R 2 = 0.848, R 2cvOO = 0.748, R 2cvMO = 0.745, F = 21.215, s 2 = 0.0002) using CODESSA-Pro software. Conclusion: These compounds can be considered as promising hits for potent bronchodilators that may be useful for further investigations. [Formula: see text]