Benzisothiazolones as modulators of macrophage migration inhibitory factor

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Jorgensen, William L.¹  Trofimov, Alexander¹  Du, Xin²  Hare, Alissa A.¹  Leng, Lin²  Bucala, Richard² 

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA

关键词: MIF inhibitors;    Benzisothiazolone;    Cysteine modification;    Macrophage migration inhibitory factor;    MIF antagonists;    Structure-based drug design;   

DOI  :  10.1016/j.bmcl.2011.05.127

来源: Elsevier

【 摘 要 】

Substituted N-phenylbenzisothiazolones have been investigated as inhibitors of the tautomerase activity of the proinflammatory cytokine MIF (macrophage migration inhibitory factor). Numerous compounds were found to possess antagonist activity in the low micromolar range with the most potent being the 6-hydroxy analog 1w. Compound 1w and the p-cyano analog 1c were also shown to exhibit significant inhibition of the binding of MIF to its transmembrane receptor CD74. Consistently, both compounds were also found to retard the MIF-dependent phosphorylation of ERK1/2 in human synovial fibroblasts. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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