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 language | English (US) |
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Pages (from-to) | 2543-2550 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 21 |
Issue number | 9 |
DOIs | |
State | Published - 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