Novel analogs of N-acylhydroxyethylaminomethyl-4H-chromen-4-one scaffold as IL-5 inhibitors

Bioorg Med Chem. 2017 Aug 15;25(16):4330-4338. doi: 10.1016/j.bmc.2017.06.018. Epub 2017 Jun 15.

Abstract

A number of N-acyl substituted hydroxyethylaminomethyl-4H-chromen-4-ones 6a-u were prepared and evaluated for their IL-5 inhibitory activity. Among them, the compound 6r (95.0% inhibition at 30µM, IC50=10.0µM, ClogP=4.1549) showed most potent inhibitory activity. The structure activity relationship revealed that the bulkier or hydrophobic substituents at urea, carbamate or amide group resulted in good inhibitory activity against IL-5. Moreover, electron donating group at phenyl ring (6g and 6s) is much more active than electron withdrawing group (6f). Finally, replacement of cyclohexylmethoxy group at 5th position of ring A with bulky aliphatic substituents resulted in the loss of activity.

Keywords: Asthma; Chromen-4-one analogs; Eosinophil; Inhibitor; Interleukin-5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Chromans / chemical synthesis
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Interleukin-5 / antagonists & inhibitors*
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Chromans
  • Interleukin-5
  • N-acylhydroxyethylaminomethyl-4H-chromen-4-one