title: Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as triple reuptake inhibitors.
abstract: A series of 3,4-diarylpyrrolidin-2-one was designed, prepared and evaluated as triple reuptake inhibitors for antidepressant. Most compounds exhibited comparable in vitro efficacy as norepinephrine and dopamine transporter reuptake inhibitors. Especially, 2i showed better potency than GBR-12909 (IC50=14 nM) which was used as reference compound for dopamine transporter. In addition, 2a and 2b showed inhibition (5.17 μM-85.6 nM) for three transporters.
authors.affiliation: Chemical Kinomics Research Center, Korea Institute of Science and Technology, Wolsong-gil 5, Seongbuk-gu, Seoul, Republic of Korea; Department of Chemistry, Sogang University, Baekbeomno 35, Mapogu, Seoul, Republic of Korea.
authors.forename: Jung-eun
authors.initials: JE
authors.lastname: Park
authors.forename: Chiman
authors.initials: C
authors.lastname: Song
authors.forename: Keehyun
authors.initials: K
authors.lastname: Choi
authors.forename: Taebo
authors.initials: T
authors.lastname: Sim
authors.forename: Bongjin
authors.initials: B
authors.lastname: Moon
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Roh
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D007769:Lactams; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011760:Pyrrolidinones; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C588143:3,4-bis(4-chlorophenyl)pyrrolidin-2-one; C588142:3-(4-chlorophenyl)-4-(3,4-dichlorophenyl)pyrrolidin-2-one
keywords: Antidepressant; Depression; Dopamine; Lactam; Monoamine; Norepinephrine; Reuptake; Serotonin; Triple reuptake inhibitors