Cirillo Pier F, Hickey Eugene R, Moss Neil, Breitfelder Steffen, Betageri Raj, Fadra Tazmeen, Gaenzler Faith, Gilmore Thomas, Goldberg Daniel R, Kamhi Victor, Kirrane Thomas, Kroe Rachel R, Madwed Jeffrey, Moriak Monica, Netherton Matthew, Pargellis Christopher A, Patel Usha R, Qian Kevin C, Sharma Rajiv, Sun Sanxing, Swinamer Alan, Torcellini Carol, Takahashi Hidenori, Tsang Michele, Xiong Zhaoming
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceutical, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Bioorg Med Chem Lett. 2009 May 1;19(9):2386-91. doi: 10.1016/j.bmcl.2009.03.104. Epub 2009 Mar 26.
An effort aimed at exploring structural diversity in the N-pyrazole-N'-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N'-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-alpha production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.
一项旨在探索p38激酶抑制剂的N-吡唑-N'-萘基脲类结构多样性的研究，促使了N-苯基-N'-萘基脲的合成与表征。这些化合物的实例在体外对TNF-α的产生表现出优异的抑制作用，并且在脂多糖诱导的内毒素血症小鼠模型中也具有疗效。此外，还阐述了磺酰胺官能团在确定抑制剂效力方面的作用。
