2. Academic Validation
  3. Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents

Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents

  • Bioorg Med Chem Lett. 2013 Nov 1;23(21):5870-3. doi: 10.1016/j.bmcl.2013.08.096.
Tsutomu Akama 1,  Chen Dong,  Charlotte Virtucio,  Yvonne R Freund,  Daitao Chen,  Matthew D Orr,  Robert T Jacobs,  Yong-Kang Zhang,  Vincent Hernandez,  Yang Liu,  Anne Wu,  Wei Bu,  Liang Liu,  Kurt Jarnagin,  Jacob J Plattner
Affiliations

Affiliation

  • 1 Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. Electronic address: [email protected].
PMID: 24075731 DOI: 10.1016/j.bmcl.2013.08.096
Abstract

Structure-activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-α, IL-1β, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC50 values between 0.19 and 0.50μM, inhibited LPS-induced TNF-α and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile.

Keywords

Anti-inflammatory; Benzoxaborole; Collagen-induced arthritis; Cytokine; Interleukin-1beta; Interleukin-6; Pharmacokinetics; Structure–activity relationships; Tumor necrosis factor-alpha.

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