756477-41-5

The present invention discloses fused thienopyridyl compounds of general formula (I), wherein X1-X6, R5-R7, Z1 and L are as defined in the description. The resent invention also discloses a method for

The synthesis and the 125I-apamin binding studies of original C-5- and C-8-substituted 1-(3,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4- tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7- tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons.

A convenient preparation of thieno[2,3-c]pyridine 3a and of several original 2-substituted-thieno[2,3-c]pyridines 3b-f is achieved by cyclization of the Schiff base resulting from the condensation between a 2- thiophenecarboxaldehyde 1a-f and aminoacetaldehyde dimethyl acetal. This procedure provides especially good yields in the case of 2-halogenated analogues.