公开(公告)号：WO2016201214A1

公开(公告)日：2016-12-15

申请号：PCT/US2016/036872

申请日：2016-06-10

Applicant: STC. UNM ,  ROSALIND FRANKLIN UNIVERSITY

Inventor： OPREA, Tudor, I. ,  BOLOGA, Cristian, George ,  URSU, Oleg ,  CHOE, Jun-Yong ,  IANCU, Cristina

IPC: C07D317/48 ,  C07D319/08 ,  C07D321/10 ,  C07D405/12 ,  C07C309/46 ,  A61K31/357 ,  A61P3/00

CPC classification number: C07D317/66 ,  A23L33/125 ,  A23V2002/00 ,  A61K31/357 ,  A61K31/36 ,  A61K45/06 ,  C07C317/36 ,  C40B30/02

Abstract: The present invention relates to compounds which have been discovered to be potent ligands (inhibitors) of human GLUT5 (glucose transporter type 5), a facilitative glucose transporter that transports fructose, and their use as ligands assays which can uncover additional ligands of GLUT5, having the potential for being used as drugs. In addition, the present invention is directed to compounds, chemical compositions and methods for treating disease states and conditions which are mediated through GLUT5, including such disease states and conditions as GLUT5 deficiency syndrome, diabetes (type I and II), cancer, metabolic diseases including metabolic syndrome and fatty liver disease, among others.

Abstract translation: 本发明涉及已被发现是人GLUT5（葡萄糖转运体5型）的有效配体（抑制剂），促进果糖的促进性葡萄糖转运体及其作为配体测定法的用途的化合物，其可以揭示GLUT5的其它配体，其具有 被用作药物的潜力。 此外，本发明涉及用于治疗通过GLUT5介导的疾病状态和病症的化合物，化学组成和方法，包括GLUT5缺乏综合征，糖尿病（I型和II型），癌症，代谢疾病 包括代谢综合征和脂肪肝疾病等。

公开(公告)号：WO2011094260A2

公开(公告)日：2011-08-04

申请号：PCT/US2011/022508

申请日：2011-01-26

Applicant: STC. UNM ,  HROMAS, Robert ,  LEITAO, Andrei ,  OPREA, Tudor, I. ,  SKLAR, Larry, A. ,  WILLIAMSON, Elizabeth, A. ,  WRAY, Justin ,  WANG, Wei

Inventor： HROMAS, Robert ,  LEITAO, Andrei ,  OPREA, Tudor, I. ,  SKLAR, Larry, A. ,  WILLIAMSON, Elizabeth, A. ,  WRAY, Justin ,  WANG, Wei

IPC: C07D215/233 ,  C07D401/04 ,  C07D401/14 ,  A61K31/47 ,  A61K31/4709 ,  A61P35/00

CPC classification number: C07D215/56 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/475 ,  A61K31/496 ,  A61K31/7048 ,  A61K45/06 ,  A61N5/1001 ,  A61N5/1045 ,  A61N2005/1087 ,  A61N2005/1098 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  A61K2300/00

Abstract: This invention relates to novel cancer treatment compositions and associated therapeutic methods. More particularly, this invention relates in part to small chemical bifunctional inhibitors of DNA replication and repair proteins Metnase and/or Intnase (also termed Gypsy Integrase, Gypsy Integrease-1, Gypsy Retransposon Integrase 1, or GIN-I) that simultaneously damage DNA, and to a therapeutic method that utilizes the inhibitors to increase the effectiveness of cancer treatment protocols, including radiation therapy. In preferred embodiments, compounds, compositions and methods of treatment of the invention are used to treat a patient suffering from leukemia (e.g. acute myeloid leukemia (AML) and related cancers. In certain aspects of such treatments, compounds, compositions and methods of treatment of the invention are administered as a monotherapy (in some cases, to patients who have exhibited resistance to Topo IIalpha inhibitors such as VP- 16), or are co-administered with a Topo IIalpha inhibitor or other anti-cancer agents as otherwise described herein or in combination with radiation therapy.

Abstract translation: 本发明涉及新的癌症治疗组合物和相关的治疗方法。 更具体地说，本发明部分涉及同时破坏DNA的DNA复制和修复蛋白Metnase和/或Intnase（也称为Gypsy整合酶，Gypsy Integrease-1，Gypsy Retransposon整合酶1或GIN-1）的小化学双功能抑制剂， 并涉及利用抑制剂来增加包括放射疗法在内的癌症治疗方案的有效性的治疗方法。 在优选的实施方案中，本发明的化合物，组合物和治疗方法用于治疗患有白血病（例如急性骨髓性白血病（AML）和相关癌症的患者）。在此类治疗的某些方面，本发明化合物，组合物和治疗 本发明作为单一疗法施用（在一些情况下，对展现对TopoIIα抑制剂如VP-16的抗性的患者），或者与本文另有描述的TopoIIα抑制剂或其它抗癌剂共同施用或 结合放射治疗。