Design and synthesis of novel chromenone derivatives as interleukin-5 inhibitors

Eeda Venkateswararao, Vinay K. Sharma, Ki Cheul Lee, Eunmiri Roh, Youngsoo Kim, Sang Hun Jung

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A novel series of chromenone analogs were synthesized and evaluated for their inhibitory activity against interleukin-5. Among them 5- (cyclohexylmethoxy)-3-[3-hydroxy-3-(4-hydroxyphenyl)propyl]-4H-chromen-4-one (9b, 94% inhibition at 30 μM, IC50 = 4.0 μM) and 5-(cyclohexylmethoxy)-3-[3-hydroxy-3-(4-methoxyphenyl)propyl]-4H-chromen-4-one (9c, 94% inhibition at 30 μM, IC50 = 6.5 μM) showed the most potent activity. According to the SAR studies introduction of propanone unit in between chromenone and ring B as in 5-(cyclohexylmethoxy)-3-[3-(4-phenyl)-3- oxopropyl]-4H-chromen-4-ones (8) moderately increased the activity. However, the reduction of these propanones 8 to propanols 9 remarkably enhanced the activity. A small substituent at position 4 of ring B in 9, especially with hydrogen bonding capability, provides favorable contribution. Disappearance of IL-5 inhibitory activity upon saturation of chroman-4-one of 9 to chroman-4-ones 10 proves the critical importance of planar chromen-4-one unit of this scaffold in the IL-5 inhibition.

Original languageEnglish (US)
Pages (from-to)2543-2550
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number9
DOIs
StatePublished - May 1 2013

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant number 2011-0014889 ).

Keywords

  • Asthma
  • Chromenone analogs
  • Eosinophils
  • Inhibitor
  • Interleukin-5

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