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

Abstract magnified image 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 = C2H5) was identified as new a potent inhibitor (IC50 = 17 μM) of this receptor subtype. The inhibitory potency of 2 (R = C2H5) against human leukocyte elastase was also examined. The compound was characterized as a noncovalent inhibitor with an IC50 value of 8.8 μM. J. Heterocyclic Chem., (2010).