CXCR3拮抗剂的研发。第3部分：托品基和高托品基哌啶脲衍生物。
Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives.
作者信息
Watson Robert J, Allen Daniel R, Birch Helen L, Chapman Gayle A, Galvin Frances C, Jopling Louise A, Knight Roland L, Meier Dorica, Oliver Kathryn, Meissner Johannes W G, Owen David A, Thomas Elizabeth J, Tremayne Neil, Williams Sophie C
机构信息
UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom.
出版信息
Bioorg Med Chem Lett. 2008 Jan 1;18(1):147-51. doi: 10.1016/j.bmcl.2007.10.109. Epub 2007 Nov 4.
The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease.
本文描述了一系列1-芳基-3-哌啶基脲衍生物的优化过程，其中引入托品基和高托品基部分使活性和类药性质得到了显著改善。用外型托品基单元取代中心哌啶，得到了化合物15，它具有对人和小鼠受体的优异活性、类药性质和药代动力学特性，从而为在人类疾病模型中评估CXCR3拮抗剂提供了一个有价值的工具。
Zotero 插件