Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives.
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.
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001692:Biological Transport / Q000187:drug effects; D008958:Models, Molecular; D009627:Nomifensine / Q000031:analogs & derivatives; D009638:Norepinephrine / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000928:Antidepressive Agents; D011725:Pyridines; D013876:Thiophenes; D009627:Nomifensine; D012701:Serotonin; D009638:Norepinephrine