Structure-activity relationships in a series of 6-thioxanthines with bronchodilator and coronary dilator properties.

The bronchodilator activity of 47 compounds on the isolated guinea-pig tracheal ring preparation and the coronary dilator activity on the dog heart-lung preparation is described. 1,3-Disubstituted xanthines and 6-thioxanthines (theophyllines and 6-thiotheophyllines) were more active as bronchodilators and as coronary dilators than were 3,7-disubstituted 6-thioxanthines (6-thiotheobromines) or 1,3,7-trisubstituted 6-thioxanthines (6-thiocaffeines). None of the 6-thioxanthines was of any interest as a diuretic and none of the 6-thiocaffeines was of any interest as a central stimulant. Structure-activity requirements for potent bronchodilator and coronary dilator activity are discussed.