title: Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT(2A) receptor and 5-HT transporter.
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.
authors.affiliation: Research Center, Green Cross Corporation, 303 Bojeong-dong, Giheung-gu, Yongin 446-770, Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Seo
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Suk Youn
authors.initials: SY
authors.lastname: Kang
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Nam
authors.initials: KN
authors.lastname: Lee
authors.forename: Myung Eun
authors.initials: ME
authors.lastname: Jung
authors.forename: Minwoo
authors.initials: M
authors.lastname: Lee
authors.forename: Mi-Soon
authors.initials: MS
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Son
authors.forename: Woo-Kyu
authors.initials: WK
authors.lastname: Park
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Kim
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D007093:Imidazoles; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors