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

J Med Chem. 1990 Nov;33(11):3110-6. doi: 10.1021/jm00173a031.

Abstract

[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 beta-carbolines and 1,2,3,4-tetrahydro-beta-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 beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemical synthesis
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Avoidance Learning / drug effects
  • Chemical Phenomena
  • Chemistry
  • Conflict, Psychological*
  • Male
  • Memory / drug effects*
  • Mice
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / metabolism
  • Receptors, Serotonin / metabolism
  • Structure-Activity Relationship
  • Sulfides / chemical synthesis
  • Sulfides / chemistry
  • Sulfides / pharmacology*
  • Thienopyridines

Substances

  • Anti-Anxiety Agents
  • Pyridines
  • Receptors, GABA-A
  • Receptors, Serotonin
  • Sulfides
  • Thienopyridines
  • N-cyclohexyl-1,2,3,4-tetrahydro(1)benzothieno(2,3-c)pyridine-3-carboxamide