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

✍ Scribed by Detlef Briel; Anastasiya Rybak; Christiane Kronbach; Klaus Unverferth; Camino M. González Tanarro; Michael Gütschow

• Book ID: 102343988
• Publisher: Journal of Heterocyclic Chemistry
• Year: 2010
• Tongue: English
• Weight: 271 KB
• Volume: 47
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.375

✦ Synopsis

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 ¼ C 2 H 5 ) was identified as new a potent inhibitor (IC 50 ¼ 17 lM) of this receptor subtype. The inhibitory potency of 2 (R ¼ 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 lM.