Potent Anticonflict Activity and Lessening of Memory Impairment with a Series of Novel Benzothienopyridines and 1,2,3,4-Tetrahydrobenzothienopyridines

Article abstract of DOI:10.1021/jm00173a031

<1>Benzothieno<2,3-c>pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-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 1,2,3,4-tetrahydro<1>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-HT_1A receptors and would be expected to be a novel anxiolytic.