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.
Jung-eun Park  1 ,  Chiman Song ,  Keehyun Choi ,  Taebo Sim ,  Bongjin Moon ,  Eun Joo Roh
Affiliations
  • 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.