公开(公告)号：US06949679B1

公开(公告)日：2005-09-27

申请号：US09529319

申请日：1998-04-21

申请人： Richard Poulin ,  Marie Audette ,  Rene Charest-Gaudrealt

发明人： Richard Poulin ,  Marie Audette ,  Rene Charest-Gaudrealt

IPC分类号： C07C211/13 ,  C07C211/22 ,  C07C211/23

CPC分类号： C07C211/22 ,  C07C211/23

摘要： The present invention describes the design, synthesis and therapeutic use of a variety of novel inhibitors of polyamine transport. The main feature of this class of transport inhibitors is to incorporate a linker or side chain that prevents the uptake of polyamines and helps to conjugate polyamine analogs to form dimers with high inhibitory potency against polyamine uptake. These new compounds incorporate features that are designed to maximize their chemical and metabolic stability and their ability to bind to the polyamine transporter, and to minimize their toxicity by preventing their absorption by the cells. The purpose of such inhibitors is to prevent the uptake or salvaging of circulating polyamines by rapidly proliferating cells such as tumor cells, in order to potentiate the effect of therapeutic inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithene.

摘要翻译： 本发明描述了多胺转运的各种新型抑制剂的设计，合成和治疗用途。 这类运输抑制剂的主要特征是引入一个阻止多胺摄取的接头或侧链，并有助于多胺类似物的结合形成具有高多胺吸收抑制效能的二聚体。 这些新化合物包含被设计为使其化学和代谢稳定性最大化的能力，以及它们与多胺转运蛋白结合的能力，并通过防止细胞吸收来最小化其毒性。 这种抑制剂的目的是通过快速增殖细胞如肿瘤细胞来防止循环多胺的摄取或回收，以增强多胺生物合成的治疗抑制剂如α-二氟甲基甲锗烷酮的作用。