title: Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.
abstract: A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure-activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile.
authors: Anacor Pharmaceuticals Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. takama@anacor.com
authors: Tsutomu
authors: T
authors: Akama
authors: Charlotte
authors: C
authors: Virtucio
authors: Chen
authors: C
authors: Dong
authors: Richard
authors: R
authors: Kimura
authors: Yong-Kang
authors: YK
authors: Zhang
authors: James A
authors: JA
authors: Nieman
authors: Rashmi
authors: R
authors: Sharma
authors: Xiaosong
authors: X
authors: Lu
authors: Marcelo
authors: M
authors: Sales
authors: Rajeshwar
authors: R
authors: Singh
authors: Anne
authors: A
authors: Wu
authors: Xiao-Qing
authors: XQ
authors: Fan
authors: Liang
authors: L
authors: Liu
authors: Jacob J
authors: JJ
authors: Plattner
authors: Kurt
authors: K
authors: Jarnagin
authors: Yvonne R
authors: YR
authors: Freund
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D001583:Benzoxazoles / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D001583:Benzoxazoles; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C579257:6-(4-(aminomethyl)-2-chlorophenoxyl)benzo(c)(1,2)oxaborol-1(3H)-ol