title: Synthesis of thieno[2,3-d]oxazines and thieno[2,3-d]thiazines as subtype specific kainate receptor antagonists.
abstract: For the development of new antiepileptics the kainate receptors GluR6 and GluR5 are important targets. Based on the anticonvulsant effects of chinazolines and thieno[2,3-d]pyrimidines that are known from the literature, thieno[2,3-d][1.3]oxazines were synthesized and studied for their inhibitory properties at GluR6 and GluR5 receptors. The strongest inhibitor activity was observed with 5-methyl-6-phenyl-thieno[2,3-d][1.3]oxazines with C1 or C3-substituents in position 2 (3b-f). The 2-trihalide-methyl-substituted compounds 3c and 3d were the most active inhibitors at the GluR5-receptor (IC50=23.4 micromol, 16 microl). The 2-isopropyl-substituted compound 3f displayed the strongest activity at the GluR6-receptor (IC(50)=8.7 micromol). A number of thieno[2,3-d][1.3]thiazines and thieno[2,3-d] pyrimidines that were synthesized from the thieno[2,3][1.3]oxazines did not show any activity.
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Brüderstrasse 34, 04103 Leipzig, Germany. briel@rz.uni-leipzig.de
authors.forename: D
authors.initials: D
authors.lastname: Briel
authors.forename: A
authors.initials: A
authors.lastname: Rybak
authors.forename: S
authors.initials: S
authors.lastname: Mann
authors.forename: C
authors.initials: C
authors.lastname: Kronbach
authors.forename: K
authors.initials: K
authors.lastname: Unverferth
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000097806:GluK2 Kainate Receptor
chemical_list: D000927:Anticonvulsants; D010078:Oxazines; D011743:Pyrimidines; D018092:Kainic Acid Receptors; D013843:Thiazines; D000097806:GluK2 Kainate Receptor