Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT(2A) receptor and 5-HT transporter.

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Seo HJ, Park EJ, Kim MJ, Kang SY, Lee SH, Kim HJ, Lee KN, Jung ME, Lee M, Kim MS, Son EJ, Park WK, Kim J, Lee J

Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT(2A) receptor and 5-HT transporter.

J Med Chem. 2011 Sep 22;54(18):6305-18. doi: 10.1021/jm200682b. Epub 2011 Aug 23.

PubMed ID

21823597 [ View in PubMed

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Abstract

Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT(2) receptors and the serotonin transporters have been developed. The human 5-HT(2A/2C) receptor has been implicated in several neurological conditions, and potent selective 5-HT(2A/2C) ligands may have therapeutic potential for treatment of CNS diseases such as depression. An imidazole moiety usually provides good pharmacokinetic properties as a drug substance, and thus considerable efforts have been devoted to develop imidazole derivatives into drug candidates. The imidazole series of compounds was evaluated against 5-HT(2A/2C) and serotonin reuptake inhibition. A few of the compounds in the series showed promising IC(50) values and antidepressant-like effect in in vivo forced swimming test (FST). On the basis of these results, further lead optimization studies resulted in identifying promising compounds potentially for therapeutic use.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aripiprazole	5-hydroxytryptamine receptor 2A	Ki (nM)	0.8	N/A	N/A	Details
Nefazodone	5-hydroxytryptamine receptor 2A	Ki (nM)	5.8	N/A	N/A	Details
Nefazodone	Sodium-dependent serotonin transporter	Ki (nM)	290	N/A	N/A	Details