Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives

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• 作者：Robert J. Watson ; Daniel R. Allen ; Helen L. Birch ; Gayle A. Chapman ; Frances C. Galvin ; Louise A. Jopling ; Rol ; L. Knight ; Dorica Meier ; Kathryn Oliver ; Johannes W.G. Meissner ; David A. Owen ; Elizabet
• 关键词：CXCR3 antagonists ; Piperidine urea ; Tropanyl urea
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：1 January 2008
• 年：2008
• 卷：18
• 期：1
• 页码：147-151
• 全文大小：214 K

文摘

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.