2,2'-[氧基二(2,1-乙二基氧基-5,2-吡啶二基)]二[6-(三氟甲氧基)-1H-苯并咪唑](AI-10-49) | 1256094-72-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2,2'-[氧基二(2,1-乙二基氧基-5,2-吡啶二基)]二[6-(三氟甲氧基)-1H-苯并咪唑](AI-10-49)
• 英文名称: 2,2'-(5,5'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(pyridine-5,2-diyl))bis(6-(trifluoromethoxy)-1H-benzo[d]imidazole)
• 英文别名: 6-(trifluoromethoxy)-2-[5-[2-[2-[6-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]pyridin-3-yl]oxyethoxy]ethoxy]pyridin-2-yl]-1H-benzimidazole
• CAS: 1256094-72-0
• 化学式: C₃₀H₂₂F₆N₆O₅
• 分子量: 660.5
• InChiKey: WJBSSBFGPKTMQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  15

文献信息

• [EN] COMBINATION THERAPIES FOR TREATING CANCER<br/>[FR] POLYTHÉRAPIES POUR LE TRAITEMENT DU CANCER
  申请人：UNIV VIRGINIA PATENT FOUNDATION

  公开号：WO2018022855A1

  公开（公告）日：2018-02-01

  This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.

  本发明涉及用于治疗inv(16)白血病的方法和组合物，特别是用于治疗急性髓细胞白血病。揭示了一种治疗inv(16)白血病的方法，包括向需要治疗的受体中施用下述治疗有效的组合物：a)式(1)化合物和b)从吡柔比星、阿柔比星、米托蒽醌、多柔比星、多诺鲁宾、伊达鲁宾、依吡鲁比星、阿糖胞苷中选择的化疗药物，以及其药学上可接受的盐和混合物。治疗有效的组合物协同抑制inv(16)白血病细胞的增殖。本发明还涉及包括化合物式(1)和化疗药物的治疗有效的组合物以及药学上可接受的载体的制药组合物。
• INHIBITORS OF INV(16) LEUKEMIA
  申请人：The University of Virginia Patent Foundation

  公开号：EP3670509A1

  公开（公告）日：2020-06-24

  This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ∼12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBFβ-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBFβ and the CBFβ-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBFβ-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBFβ-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines. Analysis of the pharmacokinetics of the developed compounds has made it possible to improve the lifetime of the compound in the plasma of mice to a level commensurate with long-term treatment.

  本发明描述了 inv(16) 融合的靶向小分子抑制剂的开发，inv(16) 融合是 12% 的急性髓性白血病（AML）的致病因子。inv（16）融合会导致患者血细胞中表达 CBFβ-SMMHC 融合蛋白。本发明提供了抑制 CBFβ 和 CBFβ-SMMHC 融合蛋白功能的化合物。这些化合物能阻断inv(16)白血病细胞系的生长，并增加其凋亡，同时对非inv(16)细胞系的影响极小。作为开发对 CBFβ-SMMHC 融合蛋白具有选择性的抑制剂的机制，本发明进一步提供了这些化合物的二聚衍生物，它们对 CBFβ-SMMHC 具有更高的效力和选择性。这些化合物对 inv(16) 白血病细胞系具有强效抑制作用，而对非 inv(16) 细胞系的影响极小。通过对所开发化合物的药代动力学分析，可以将化合物在小鼠血浆中的存活时间延长到与长期治疗相称的水平。
• Combination therapies for treating cancer
  申请人：UNIVERSITY OF VIRGINIA PATENT FOUNDATION

  公开号：US11241421B2

  公开（公告）日：2022-02-08

  This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.

  本发明涉及治疗inv(16)白血病，特别是急性髓性白血病的方法和组合物。本发明公开了一种治疗 inv(16)白血病的方法，包括向有需要的受试者施用 a) 式（1）化合物和 b) 选自吡柔比星、阿克拉比星、米托蒽醌、多柔比星、达乌诺比星、依达比星、表柔比星、阿糖胞苷、阿糖胞苷、药学上可接受的盐及其混合物的化疗剂的治疗有效组合物。治疗有效的组合能协同抑制 inv(16) 白血病细胞的增殖。本发明还涉及药物组合物，其中包含式（1）化合物和化疗剂的治疗有效组合物以及药学上可接受的赋形剂。
• COMBINATION THERAPIES FOR TREATING CANCER
  申请人：UNIVERSITY OF VIRGINIA PATENT FOUNDATION

  公开号：US20190343820A1

  公开（公告）日：2019-11-14

  This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.
• METHODS FOR INDUCING HEMATOPOIETIC STEM CELL SPECIFICITY
  申请人：THE CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US20200362308A1

  公开（公告）日：2020-11-19

  Described herein are methods for inducing HSC specification in a cell. Aspects of the invention relate to contacting a cell with a Runx1-CBFβ inhibitor for a specified period of time, and then removing the inhibitor from the cell. In some embodiments of any of the aspects, HSC specificity is maintained long-term.