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

Publication date: 15 August 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 16
Author(s): Hyun-Sun Yang, Eeda Venkateswararao, Pulla Reddy Boggu, Vinay K. Sharma, Youngsoo Kim, Sang-Hun Jung
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 5^th position of ring A with bulky aliphatic substituents resulted in the loss of activity.

Graphical abstract

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