2-烷基氨基和烷氧基取代的2-氨基-1,3,4-恶二唑-O-烷基苯甲羟肟酸酯替代物保留了对MEK（丝裂原活化蛋白激酶激酶）所需的抑制作用和选择性。
2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase).
作者信息
Warmus Joseph S, Flamme Cathlin, Zhang Lu Yan, Barrett Stephen, Bridges Alexander, Chen Huifen, Gowan Richard, Kaufman Michael, Sebolt-Leopold Judy, Leopold Wilbur, Merriman Ronald, Ohren Jeffrey, Pavlovsky Alexander, Przybranowski Sally, Tecle Haile, Valik Heather, Whitehead Christopher, Zhang Erli
机构信息
Department of Chemistry, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
出版信息
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6171-4. doi: 10.1016/j.bmcl.2008.10.015. Epub 2008 Oct 7.
This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.
本文报道了一种第二代MEK抑制剂。先前报道的强效且有效的MEK抑制剂PD - 184352（CI - 1040）含有一个完整的异羟肟酸部分。该化合物存在溶解度和代谢稳定性不尽人意的问题。一个恶二唑部分可作为异羟肟酸基团的生物电子等排体，从而产生一种代谢更稳定且有效的MEK抑制剂。
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