Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives

• Published in: Journal of medicinal chemistry 1984-09, Vol.27 (9), p.1150-1155
• Main Authors: Schneider, Claus S, Weber, Karl H, Daniel, Helmut, Bechtel, Wolf D, Boeke-Kuhn, Karin
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - chemical synthesis; Biological Transport - drug effects; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Models, Molecular; Nomifensine - analogs & derivatives; Norepinephrine - metabolism; Organic chemistry; Preparations and properties; Pyridines - chemical synthesis; Pyridines - pharmacology; Rats; Serotonin - metabolism; Structure-Activity Relationship; Thiophenes - chemical synthesis; Thiophenes - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00375a011

A series of substituted 4-aryltetrahydrothieno[2,3-c]pyridines was prepared by acid-catalyzed cyclization of 1-aryl-2-[(2-thienylmethyl)amino]ethanol derivatives. The compounds were examined for their antidepressant activity, as demonstrated by their ability to inhibit the uptake of norepinephrine (NE) and serotonin (5-HT) and to prevent tetrabenazine-induced ptosis (TBZ) in mice. Significant inhibition of both neurotransmitters is observed for several of the tested compounds, while some of them are selective inhibitors of either NE or 5-HT uptake. Optimal activity is associated with the introduction of lipophilic substituents into the 4-position of the phenyl ring and less lipophilic substituents into the 2-position of the thiophene ring (11, 23). Compound 33 bearing substituents in positions 2 and 6 of the phenyl ring is inactive. This might be a consequence of an out of plane conformation of this compound.