Design and synthesis of novel hydroxyalkylaminomethylchromones for their IL-5 inhibitory activity

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 13; pp. 4625 - 4629
• Main Authors: Thanigaimalai, P., Lee, Ki-Cheul, Sharma, Vinay K., Yun, Jun-Ho, Kim, Youngsoo, Jung, Sang-Hun
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.07.2010; Elsevier
• Subjects: Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; Chromones - chemical synthesis; Chromones - chemistry; Chromones - pharmacology; Drug Design; Humans; Hydrophobic and Hydrophilic Interactions; Hydroxyalkylaminomethylchromone; Inhibitors; Interleukin-5; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - metabolism; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; Hydroxyalkylaminomethylchromone; Interleukin-5; Inhibitors; Aminoalcohol; Interleukin 5; Chromone derivatives; Inhibitor; Chemical synthesis; Biological activity; Lipophilicity; Physicochemical properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.05.028

A new series of hydroxyalkylaminomethylchromones 3( a– p) were synthesized and demonstrated for their activity against intrerlukin-5. The most active analog 3d inhibited interleukin-5 activity with an IC 50 of 17.5 μM. A series of hydroxyalkylaminomethylchromone analogs 3 were prepared and evaluated as inhibitors of interleukin-5. The most active analog 3d inhibited interleukin-5 activity with an IC 50 of 17.5 μM. The structural requirements of chromone analogs possessing the inhibitory activity against IL-5 could be summarized as: (i) the cyclohexylmethoxy group at 5th position of the A ring, (ii) the planarity of chromone ring, (iii) hydrophobic unit around the B ring with hydroxyl functional group, (iv) the hydrophobic unit which does not have to be a planar and (v) the length of carbon units between amino and hydroxyl group is limited to two.