Thieno[2,3‐ d ]pyrimidines and ‐[1,3]oxazines as glutamate antagonists and investigations on the inhibitory potency toward human leukocyte elastase

A series of fused thiophene derivatives, that is, representatives of thieno[2,3‐ d ]pyrimidines, thieno[2,3‐ d ][1, 3]oxazines and thieno[2,3‐ d ][1, 3]thiazines, with the common 5‐methyl‐6‐phenyl substitution pattern was synthesized. The target compounds, e.g ., 7 or 8 , were designed as cyclic analogs of ethyl 2‐amino‐4‐methyl‐5‐phenylthiophene‐3‐carboxylate, an antagonist at the GluR6 kainate receptor. Thieno[2,3‐ d ][1, 3]oxazin‐4‐one 2 (R = C 2 H 5 ) was identified as new a potent inhibitor (IC 50 = 17 μ M ) of this receptor subtype. The inhibitory potency of 2 (R = C 2 H 5 ) against human leukocyte elastase was also examined. The compound was characterized as a noncovalent inhibitor with an IC 50 value of 8.8 μ M . J. Heterocyclic Chem., (2010).