-
公开(公告)号：US06949679B1
公开(公告)日：2005-09-27
申请号：US09529319
申请日：1998-04-21
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。
-
公开(公告)号：US20050267220A1
公开(公告)日：2005-12-01
申请号：US11128199
申请日：2005-05-13
IPC分类号： A61K31/13
CPC分类号： A61K31/13
摘要： A method for inhibiting the activity of a natural polyamine transporter comprising the step of contacting the transporter with an inhibitorily effective amount of a compound of formula (I) or (II): wherein L is a linker; R1=H, methyl, ethyl or propyl; R2=H or methyl; 0
摘要翻译： 一种抑制天然多胺转运蛋白活性的方法，包括使转运蛋白与抑制有效量的式（I）或（II）化合物接触的步骤：其中L为连接基; R 1 = H，甲基，乙基或丙基; R 2 = H或甲基; 0
-
公开(公告)号：US07425579B2
公开(公告)日：2008-09-16
申请号：US11128199
申请日：2005-05-13
IPC分类号： A61K31/165
CPC分类号： A61K31/13
摘要： A method for inhibiting the activity of a natural polyamine transporter comprising the step of contacting the transporter with an inhibitorily effective amount of a compound of formula (I) or (II): wherein L is a linker; R1=H, methyl, ethyl or propyl; R2=H or methyl; 0
摘要翻译： 一种抑制天然多胺转运蛋白活性的方法，包括使转运蛋白与抑制有效量的式（I）或（II）化合物接触的步骤：其中L为连接基; R 1 = H，甲基，乙基或丙基; R 2 = H或甲基; 0
-
公开(公告)号：US06083496A
公开(公告)日：2000-07-04
申请号：US735130
申请日：1996-10-22
IPC分类号： C07C211/14 , C07C237/10 , C07C323/41 , A61K31/74 , A61K31/765 , A61K31/785
CPC分类号： C07C323/41 , C07C211/14 , C07C237/10
摘要： Described herein are novel specific, pure competitive inhibitors of natural polyamine transport in mammalian cells. Despite their low molecular weight, the inhibitors of the present invention stay virtually impermeant to the cell and display minor non-specific effects while exhibiting a very high affinity for the carrier. More specifically described are synthetic derivatives of original polyamines, wherein the original polyamine is modified to comprise an amido group immediately linked to the polyamine backbone. A side chain may be anchored to the amido group and provide for the formation of dimeric synthetic derivatives or its labelling and subsequent usage as a marker for the polyamine transporter. The use of such novel inhibitors of polyamine transport to evaluate the antitumor efficacy of polyamine depletion strategies with minimal systemic cytotoxic effects or to control and treat disorders involving unrestrained cell proliferation and/or cell differentiation wherein polyamine transport is required as well as pharmaceutical composition thereof are also described.
摘要翻译： 本文描述的是哺乳动物细胞中天然多胺转运的新型特异性纯竞争性抑制剂。 尽管它们的分子量低，但是本发明的抑制剂对细胞几乎是不渗透的，并且显示出非常小的特异性效应，同时对载体表现出非常高的亲和力。 更具体地描述了原始多胺的合成衍生物，其中原始多胺被修饰为包含立即连接到多胺主链的酰氨基。 侧链可以锚定到酰氨基上，并提供形成二聚合成衍生物或其标记和随后用作多胺转运蛋白的标记物。 使用这种多胺转运的这种新型抑制剂以最小的全身细胞毒性作用来评估多胺消耗策略的抗肿瘤功效，或者控制和治疗涉及需要多胺转运的无限制细胞增殖和/或细胞分化的疾病以及其药物组合物 也描述。
-
-
-
搜索结果
4 条记录 (耗时 0.024 秒)
