A bstracl: New tricyclic heterocycles, 911-s-~lo13.4-ilpurin-5ounes(2, 31, wemprepared from 6-methylthio-7H-purin-2o_ones (5a, Sd)
Theophylline (1) is currently recognized as a drug of choice for the maintenance therapy of asthma.' However, theophylhne has a narrow optimum therapeutic range due to its side effects such as central nervous system stimulation, canliotonic activity and emesis2
As a part of our ongoing efforts to screen for superior analogs of theophylline, we have studied the synthesis and pharmacological activity of new tricyclic heterocycles such as W-s-triazolo[3,4-llpurin-5(6H)-ones.
Among them, compounds 2 and 3 were recently found to exhibit 5-to lOO-fold more potent bronchodilatory activity than theophylline.3
This discavery prompted us to devise facile and general synthesis of such heterocycles.
Entry to those molecular systems and their derivatives are of interest, not only in terms of their potent bronchodilatory activities, but also structurally defined probes for multibiological reactions of theophylline.
This communication reports a synthesis of this unique ring system starting from 6methylthio-7H-purin2(3H)-ones @a, 5 d), which are readily available from 6-thioxanthines.