Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as triple reuptake inhibitors

Jung-eun Park; Chiman Song; Keehyun Choi; Taebo Sim; Bongjin Moon; Eun Joo Roh

doi:10.1016/j.bmcl.2013.08.062

Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as triple reuptake inhibitors

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5515-8. doi: 10.1016/j.bmcl.2013.08.062. Epub 2013 Aug 26.

Authors

Jung-eun Park¹, Chiman Song, Keehyun Choi, Taebo Sim, Bongjin Moon, Eun Joo Roh

Affiliation

¹ 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.

PMID: 24012181
DOI: 10.1016/j.bmcl.2013.08.062

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.

Keywords: Antidepressant; Depression; Dopamine; Lactam; Monoamine; Norepinephrine; Reuptake; Serotonin; Triple reuptake inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic Uptake Inhibitors / chemical synthesis*
Adrenergic Uptake Inhibitors / chemistry
Adrenergic Uptake Inhibitors / metabolism
Antidepressive Agents / chemical synthesis
Antidepressive Agents / chemistry
Antidepressive Agents / metabolism
Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
Dopamine Plasma Membrane Transport Proteins / metabolism
Dopamine Uptake Inhibitors / chemical synthesis*
Dopamine Uptake Inhibitors / chemistry
Dopamine Uptake Inhibitors / metabolism
Humans
Lactams / chemical synthesis
Lactams / chemistry*
Lactams / metabolism
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors
Norepinephrine Plasma Membrane Transport Proteins / metabolism
Protein Binding
Pyrrolidinones / chemical synthesis*
Pyrrolidinones / chemistry
Pyrrolidinones / metabolism
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Selective Serotonin Reuptake Inhibitors / chemistry
Selective Serotonin Reuptake Inhibitors / metabolism
Serotonin Plasma Membrane Transport Proteins / chemistry
Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

3,4-bis(4-chlorophenyl)pyrrolidin-2-one
3-(4-chlorophenyl)-4-(3,4-dichlorophenyl)pyrrolidin-2-one
Adrenergic Uptake Inhibitors
Antidepressive Agents
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors
Lactams
Norepinephrine Plasma Membrane Transport Proteins
Pyrrolidinones
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors