1-[3-[(6-oxo-6H-imidazo[4.5.1-de]acridin-5-yl)amino]propyl]-4-(3-aminopropyl)piperazine | 251911-90-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-[3-[(6-oxo-6H-imidazo[4.5.1-de]acridin-5-yl)amino]propyl]-4-(3-aminopropyl)piperazine
• 英文别名: 5-{3-[(4-(3-aminopropyl)piperazin-1-yl)]propylamino}-2,10b-diaza-aceanthrylen-6-one；5-((3-(4-(3-Aminopropyl)-1-piperazinyl)propyl)amino)-6H-imidazo[4,5,1-de]acridin-6-one hydrochloride；10-[3-[4-(3-aminopropyl)piperazin-1-yl]propylamino]-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16),14-heptaen-8-one
• CAS: 251911-90-7
• 化学式: C₂₄H₃₀N₆O
• 分子量: 418.542
• InChiKey: LGLBFPWUUGZYBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[3-[(6-oxo-6H-imidazo[4.5.1-de]acridin-5-yl)amino]propyl]-4-(3-aminopropyl)piperazine 在 盐酸 、 溶剂黄146 、 tin(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-{3-{4-[3-(6-oxo-6H-imidazo[4,5,1-de]acridin-5-yl)aminopropyl]piperazin-1-yl}-propyl}-5-amino-1H-benz[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  A New Synthetic Agent with Potent but Selective Cytotoxic Activity against Cancer

  摘要：

  The synthesis of novel unsymmetrical bifunctional antitumor agents was accomplished by linking an imidazoacridone moiety to another polycyclic heteroaromatic moiety via linkers of various length and rigidity. These compounds bind to cellular DNA, but it is hypothesized that biological effects become manifested when the drug-DNA complexes interact with critical DNA binding proteins that are involved in repair and transcription. The most promising compound of the series, 4ad (WMC79), consists of an imidazoacridone linked to a 3-nitronaph-thalimide moiety via a 1,4-dipropanopiperazine linker. It was found to be potently, but selectively, cytotoxic against colon cancers (GI(50) = 0.5 nM, LC50 = 32 nM) and leukemias (GI(50) = 3.5 nM, LC50 = 33 nM). Compound 4ad, which appears to be a candidate for further development as an anticancer drug, kills sensitive cells by induction of apoptosis. It also showed significant in vivo activity against HCT-116 colon cancer xenografts in nude mice. Other compounds in the series also exhibited antitumor properties, but they were significantly lower than that of 4ad.

  DOI：

  10.1021/jm048946x
• 作为产物：
  描述：

  1,4-双(3-氨基丙基)哌嗪 在 镍 盐酸 、 氢气 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 1-[3-[(6-oxo-6H-imidazo[4.5.1-de]acridin-5-yl)amino]propyl]-4-(3-aminopropyl)piperazine
  参考文献：
  名称：

  Bisimidazoacridones：分子环境对构象和光物理性质的影响

  摘要：

  Bisimidazoacridones (BIA) 是高度选择性的抗肿瘤和抗病毒药物。进行了紫外可见光谱和稳态和时间分辨荧光光谱研究，以探测 BIA 在水性和非水性（有机溶剂、胶体胶束）溶液中的行为。揭示了三个荧光寿命范围：~0.2-0.5 ns（大概反映发色团-生色团相互作用）、~1-5 ns（解释为连接子扰动的发色团衰减）和~6-12 ns（未受干扰的发色团衰减）。这些成分对衰减信号的指数前和稳态贡献以及稳态荧光​​强度数据，波长最大值和带宽表明，溶液中的 BIA 构象对环境敏感，并受到它们使疏水相互作用最小化的倾向的强烈影响。在水中，分子倾向于采用缩合构象，使两个亚胺-偶氮吖啶酮部分靠近（导致分子内荧光能量转移），而在非水系统中，构象变得更加松弛。大分子从极性环境向更亲脂环境的转移被认为是 BIA 与生物大分子（如核酸）结合的主要驱动力。而在非水系统中，构象变得更加松弛。大分子从极性环境向更亲脂环境的转移被认为是

  DOI：

  10.1111/j.1751-1097.1999.tb08253.x

文献信息

• Smoothened polypeptides and methods of use
  申请人：Government of the United States of America, Represented by the Secretary, Department of Health and Human Services

  公开号：EP2431388A1

  公开（公告）日：2012-03-21

  Disclosed is an isolated or purified polypeptide or peptidomimetic comprising an amino acid sequence of a portion of a Smoothened (SMO) protein, wherein the portion comprises an amino acid sequence of any of the intracellular loops of the SMO protein, a functional fragment thereof, or a functional variant of either the portion or the functional fragment, wherein the functional fragment comprises at least 7 contiguous amino acids of the intracellular loops, and wherein the functional fragment or functional variant inhibits proliferation of a diseased cell, or a fatty acid derivative thereof. Related conjugates, nucleic acids, recombinant expression vectors, host cells, and pharmaceutical compositions are further provided. Methods of inhibiting proliferation of a diseased cell, treating or preventing cancer, treating a neoplasm or psoriasis, and inhibiting the expression of genes involved in the Hedgehog signaling pathway, thereby inhibiting the Hedgehog signaling pathway, are furthermore provided by the invention.

  本发明公开了一种分离或纯化的多肽或仿肽物，其包含 Smoothened（SMO）蛋白部分的氨基酸序列，其中该部分包含 SMO 蛋白细胞内环的任何一个氨基酸序列、其功能片段、或该部分或功能片段的功能变体，其中功能片段包括细胞内环的至少 7 个连续氨基酸，且功能片段或功能变体可抑制病变细胞的增殖，或其脂肪酸衍生物。还提供了相关的共轭物、核酸、重组表达载体、宿主细胞和药物组合物。本发明还进一步提供了抑制病变细胞增殖、治疗或预防癌症、治疗肿瘤或牛皮癣以及抑制参与刺猬信号通路的基因表达从而抑制刺猬信号通路的方法。
• Optimization of Naphthalimide-imidazoacridone with Potent Antitumor Activity Leading to Clinical Candidate (HKH40A, RTA 502)
  作者：Humcha K. Hariprakasha、Teresa Kosakowska-Cholody、Colin Meyer、Wieslaw M. Cholody、Sherman F. Stinson、Nadya I. Tarasova、Christopher. J. Michejda

  DOI：10.1021/jm7009777

  日期：2007.11.1

  Unsymmetrical bifunctional antitumor agent WMC79 was further optimized to generate compound 7b that not only inhibited the growth of many tumor cell lines, but caused rapid apoptosis. Unlike the parent compound, 7b is toxic to both p53 positive and negative cancer cells. It. has potent in vivo activity against xenografts of human colon and pancreatic tumors in athymic mice.
• SELF-ASSEMBLING NANOPARTICLES COMPOSED OF TRANSMEMBRANE PEPTIDES AND THEIR APPLICATION FOR SPECIFIC INTRA-TUMOR DELIVERY OF ANTI-CANCER DRUGS
  申请人：Government of the United States of America, Represented by the Secretary, Department of Health and Human Services

  公开号：EP2086521A2

  公开（公告）日：2009-08-12
• SMOOTHENED POLYPEPTIDES AND METHODS OF USE
  申请人：Government of the United States of America, Represented by the Secretary, Department of Health and Human Services

  公开号：EP2078036A2

  公开（公告）日：2009-07-15
• US8198402B2
  申请人：——

  公开号：US8198402B2

  公开（公告）日：2012-06-12