Identification of optically active pyrimidine derivatives as selective 5-HT2C modulators

Juhyeon Kim, Hanbyeol Jo, Hyunseung Lee, Hyunah Choo, Hak Joong Kim, Ae Nim Pae, Yong Seo Cho, Sun Joon Min

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes.

Original languageEnglish
Article number1416
JournalMolecules
Volume22
Issue number9
DOIs
Publication statusPublished - 2017 Sep

Keywords

  • 5-HT2C receptor
  • Binding affinity
  • Enzymatic kinetic resolution
  • Optically active
  • Pyrimidine
  • Selectivity

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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  • Cite this

    Kim, J., Jo, H., Lee, H., Choo, H., Kim, H. J., Pae, A. N., Cho, Y. S., & Min, S. J. (2017). Identification of optically active pyrimidine derivatives as selective 5-HT2C modulators. Molecules, 22(9), [1416]. https://doi.org/10.3390/molecules22091416