4-(3,5-bis(benzyloxy)phenyl)-6-(5-chloro-2-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile | 1453835-43-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(3,5-bis(benzyloxy)phenyl)-6-(5-chloro-2-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 4-[3,5-Bis(benzyloxy)phenyl]-6-(5-chloro-2-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile；4-[3,5-bis(phenylmethoxy)phenyl]-6-(5-chloro-2-hydroxyphenyl)-2-oxo-1H-pyridine-3-carbonitrile
• CAS: 1453835-43-2
• 化学式: C₃₂H₂₃ClN₂O₄
• 分子量: 534.999
• InChiKey: NZRBRJQYGLEINZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-羟基-5-氯苯乙酮 、 3,5-二苄氧基苯甲醛 、 氰乙酸乙酯 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 以32%的产率得到4-(3,5-bis(benzyloxy)phenyl)-6-(5-chloro-2-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile
  参考文献：
  名称：

  Design, synthesis and biological studies of Survivin Dimerization Modulators that prolong mitotic cycle

  摘要：

  Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins, has essential roles in cell division and inhibition of apoptosis. Several clinical studies in cancer patients have shown that the elevated levels of survivin correlate with aggressiveness of the disease and resistance to radiation and chemotherapeutic treatments. Survivin is an integral component of chromosomal passenger complex (CPC) where it binds to borealin and INCENP through its dimerization interface. Thus, disruption of functional survivin along its dimer interface with a small molecule is hypothesized to inhibit the proliferation of cancer cells and sensitize them to therapeutic agents and radiation. Recently, a small molecule (Abbott8) was reported to bind at the dimerization interface of survivin. Further development of this compound was accomplished by computational modeling of the molecular interactions along the dimerization interface, which has led to the design of promising survivin dimerization modulators. Two of the most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and 100 nM, caused delay in mitotic progression and major mitotic defects in proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer cells (PC3). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.034

文献信息

• METHOD FOR PREPARING AND DELIVERING BISANTRENE FORMULATIONS
  申请人：Race Oncology Ltd.

  公开号：EP3860575A1

  公开（公告）日：2021-08-11
• [EN] METHOD FOR PREPARING AND DELIVERING BISANTRENE FORMULATIONS<br/>[FR] PROCÉDÉ DE PRÉPARATION ET D'ADMINISTRATION DE FORMULATIONS DE BISANTRÈNE
  申请人：RACE ONCOLOGY LTD

  公开号：WO2020072948A1

  公开（公告）日：2020-04-09

  The present invention is directed to an improved method for preparing bisantrene, specifically bisantrene dihydrochloride, for intravenous administration, as well as to preparations of bisantrene dihydrochloride for intravenous administration. The present invention is also directed to methods for treatment of malignancies treatable by administration of bisantrene, which can include administration of additional anti-neoplastic agents, wherein the bisantrene is prepared by a method according to the present invention.
• Design, synthesis and biological studies of Survivin Dimerization Modulators that prolong mitotic cycle
  作者：Somsundaram N. Chettiar、James V. Cooley、In-Hee Park、Deepak Bhasin、Arnab Chakravarti、Pui-Kai Li、Chenglong Li、Naduparambil Korah Jacob

  DOI：10.1016/j.bmcl.2013.07.034

  日期：2013.10

  Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins, has essential roles in cell division and inhibition of apoptosis. Several clinical studies in cancer patients have shown that the elevated levels of survivin correlate with aggressiveness of the disease and resistance to radiation and chemotherapeutic treatments. Survivin is an integral component of chromosomal passenger complex (CPC) where it binds to borealin and INCENP through its dimerization interface. Thus, disruption of functional survivin along its dimer interface with a small molecule is hypothesized to inhibit the proliferation of cancer cells and sensitize them to therapeutic agents and radiation. Recently, a small molecule (Abbott8) was reported to bind at the dimerization interface of survivin. Further development of this compound was accomplished by computational modeling of the molecular interactions along the dimerization interface, which has led to the design of promising survivin dimerization modulators. Two of the most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and 100 nM, caused delay in mitotic progression and major mitotic defects in proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer cells (PC3). (C) 2013 Elsevier Ltd. All rights reserved.