| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1393989 | European Journal of Medicinal Chemistry | 2015 | 10 Pages |
•LCAP with cyclic amino acid amides.•Homology modeling and docking to 5-HT1A and 5-HT7Rs.•5-HT7 antagonist.•5-HT1A partial agonist.•Depression.
A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT7Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970.
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