title: Exploration of benzamidochromenone derivatives with conformational restrictor as interleukin-5 inhibitors.
abstract: Novel amidochromen-4-one analogs 8a-k and 9a-f were prepared and studied for their IL-5 inhibitory activity. Among the synthesized compounds, (6-benzamido-2-cyclohexyl-4-oxo-4H-chromen-3-yl)methyl acetate (8a, 95% inhibition at 30 μM, IC50=6.1 μM) exhibited potent IL-5 inhibitory activity. The conformational restrictor at position 2 like bulky cyclohexyl group is favorable for the formation of effective conformer of side chain small ester like acetoxymethyl at position 3 of these chromenone analogs 8. In addition the hydrophobic planarity of benzamido group at position 6 should be important for the potent IL-5 inhibitory activity. Since replacing acetoxymethyl moiety with hydroxymethyl group at position 3 of chromenone decreases the activity, which indicates that the location of hydrogen bonding group should be near 4 atom distances away from chromenone ring is more optimum for the activity. Therefore, these benzamidochromen-4-one analogs 8 are novel scaffold for finding potent interleukin-5 inhibitors.
authors: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Eeda
authors: E
authors: Venkateswararao
authors: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Manoj
authors: M
authors: Manickam
authors: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Pullareddy
authors: P
authors: Boggu
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Youngsoo
authors: Y
authors: Kim
authors: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: jungshh@cnu.ac.kr.
authors: Sang-Hun
authors: SH
authors: Jung
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D018927:Anti-Asthmatic Agents; D001578:Benzopyrans; C508599:IL5 protein, human; D007155:Immunologic Factors; D015848:Interleukin-5
keywords: Benzamidochromenone; Conformational restrictor; Eosinophils; Inhibitor; Interleukin-5