title: Design and synthesis of novel chromenone derivatives as interleukin-5 inhibitors.
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, IC(50) = 4.0 μM) and 5-(cyclohexylmethoxy)-3-[3-hydroxy-3-(4-methoxyphenyl)propyl]-4H-chromen-4-one (9c, 94% inhibition at 30 μM, IC(50) = 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.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Eeda
authors.initials: E
authors.lastname: Venkateswararao
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Ki-Cheul
authors.initials: KC
authors.lastname: Lee
authors.forename: Eunmiri
authors.initials: E
authors.lastname: Roh
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002867:Chromones; D015848:Interleukin-5