Identification of some novel xanthine-based derivatives with bronchodilator activity.

Abstract

The discovery of new bronchodilators with higher efficacy than theophylline is an important issue for asthmatic patients. 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. 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. These compounds can be considered as promising hits for potent bronchodilators that may be useful for further investigations. [Formula: see text].