Synthesis, potency, and in vivo evaluation of 2-piperazin-1-ylquinoline analogues as dual serotonin reuptake inhibitors and serotonin 5-HT1A receptor antagonists.

On the basis of the previously reported clinical candidate, SSA-426 (1), a series of related 2-piperazin-1-ylquinoline derivatives 3-16 were synthesized and evaluated as dual-acting serotonin (5-HT) reuptake inhibitors and 5-HT1A receptor antagonists. In particular, compound 7 exhibits potent functional activities at both the 5-HT transporter and 5-HT1A receptor, good selectivity over the alpha1-adrenergic and dopaminergic receptors, acceptable pharmacokinetic properties, and a favorable in vivo profile.

Citation

Dahui Zhou, Gary P Stack, Jennifer Lo, Amedeo A Failli, Deborah A Evrard, Boyd L Harrison, Nicole T Hatzenbuhler, Megan Tran, Susan Croce, Soo Yi, Jeannette Golembieski, Geoffrey A Hornby, Margaret Lai, Qian Lin, Lee E Schechter, Deborah L Smith, Adam D Shilling, Christine Huselton, Paul Mitchell, Chad E Beyer, Terrance H Andree. Synthesis, potency, and in vivo evaluation of 2-piperazin-1-ylquinoline analogues as dual serotonin reuptake inhibitors and serotonin 5-HT1A receptor antagonists. Journal of medicinal chemistry. 2009 Aug 13;52(15):4955-9

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PMID: 19719241

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