Bioorganic & Medicinal Chemistry Letters 2013-03-15

Structure-activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent.

Tsutomu Akama, Charlotte Virtucio, Chen Dong, Richard Kimura, Yong-Kang Zhang, James A Nieman, Rashmi Sharma, Xiaosong Lu, Marcelo Sales, Rajeshwar Singh, Anne Wu, Xiao-Qing Fan, Liang Liu, Jacob J Plattner, Kurt Jarnagin, Yvonne R Freund

Index: Bioorg. Med. Chem. Lett. 23(6) , 1680-3, (2013)

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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.Copyright © 2013 Elsevier Ltd. All rights reserved.