POTENT ANTICONFLICT ACTIVITY AND LESSENING OF MEMORY IMPAIRMENT WITH A SERIES OF NOVEL [1]BENZOTHIENO[2,3-C]PYRIDINES AND 1,2,3,4-TETRAHYDRO[1]BENZOTHIENO[2,3-C]PYRIDINES

[1]Benzothieno[2,3-c]pyridines (10a-c, 11,12a-t, and 13a,b) and l,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of β-carbolines and 1,2,3,4-tetrahydro-β-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the l,2,3,4-tetrahydro[l]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno[2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of β-carbolines. Compound 7 bound strongly to 5-HT1Areceptors and would be expected to be a novel anxiolytic. © 1990, American Chemical Society. All rights reserved.