3,6-二氨基-9-吖啶酮 | 42832-87-1

• 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
• 中文名称: 3,6-二氨基-9-吖啶酮
• 英文名称: 3,6-diaminoacridone
• 英文别名: 3,6-bisaminoacridone；3,6-diaminoacridin-9(10H)-one；3,6-diamino-10H-acridin-9-one；3,6-Diamino-10H-acridin-9-on；3,6-diamino-9(10H)-acridone；3,6-diamino-10H-acridin-9-one
• CAS: 42832-87-1
• 化学式: C₁₃H₁₁N₃O
• 分子量: 225.25
• InChiKey: KKKYRANCRKCGDB-UHFFFAOYSA-N

物化性质

• 熔点：
  >300°C dec.
• 沸点：
  523.9±50.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（稍微加热）、甲醇（非常轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.1
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

制备方法与用途

3,6-二氨基-9(10H)-吖啶酮是一种拓扑异构酶抑制剂。

反应信息

• 作为反应物：
  描述：

  3,6-二氨基-9-吖啶酮 在 sodium carbonate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 28.0h， 生成 N-[9-(4-dimethylamino-phenylamino)-6-(3-pyrrolidin-1-yl-propionylamino)-acridin-3-yl]-3-pyrrolidin-1-yl-propionamide
  参考文献：
  名称：

  Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents

  摘要：

  The design, synthesis, biophysical and biochemical evaluation is presented of a new series of benzylamino-substituted acridines as G-quadruplex binding telomerase inhibitors. Replacement of the previously reported anilino substituents by benzylamino groups results in enhanced quadruplex interaction, and for one compound, superior telomerase inhibitory activity. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.01.056
• 作为产物：
  描述：

  4-acetylamino-2-(3-amino-anilino)-benzoic acid 在 硫酸 作用下， 生成 3,6-二氨基-9-吖啶酮
  参考文献：
  名称：

  29.二氨基ac啶的合成。第一部分

  摘要：

  DOI：

  10.1039/jr9460000102

文献信息

• Synthesis and in vitro Evaluation of 9-Anilino-3,6-diaminoacridines Active Against a Multidrug-Resistant Strain of the Malaria Parasite Plasmodium falciparum
  作者：Swarna A. Gamage、Nisana Tepsiri、Prapon Wilairat、Stanley J. Wojcik、David P. Figgitt、Raymond K. Ralph、William A. Denny

  DOI：10.1021/jm00036a014

  日期：1994.5

  A new synthesis of 3,6-diamino-9-anilinoacridines, via reduction of the corresponding diazides, gives much higher yields than traditional methods. Within the subset of 3,6-diamino-9-anilinoacridines, there was considerable tolerance to substitution at the 1'-anilino position. In a sharp divergence with structure-activity relationships for high mammalian cell toxicity and anticancer effects, derivatives

  已经制备了一系列9-苯胺基oa啶酮，并评估了它们对红细胞悬液中疟原虫恶性疟原虫的多药耐药K1株的活性。与其他取代方式相比，啶环上的3,6-二氨基取代导致较低的哺乳动物细胞细胞毒性和较高的抗寄生虫活性，从而提供具有最高体外治疗指数的化合物。通过还原相应的叠氮化物，新合成3,6-二氨基-9-苯胺基cr啶的产率比传统方法高得多。在3，6-二氨基-9-苯胺基cr啶的子集中，对1'-苯胺基位置的取代具有相当大的耐受性。在具有高哺乳动物细胞毒性和抗癌作用的构效关系方面，带有吸电子1'取代基的衍生物（例如SO2-NHR和CONHR）显示出最有效的抗疟活性（IC50值为10-20 nM）。代表性的化合物显示出是人类拓扑异构酶II的DNA链传递活性和相应寄生虫DNA脱链活性的有效抑制剂。1'-SO2NH2衍生物7n在20 microM时完全抑制了Jurkat拓扑异构酶II的链通过，并且在1 microM或以
• Therapeutic acridone and acridine compounds
  申请人：——

  公开号：US20030207909A1

  公开（公告）日：2003-11-06

  The present invention pertains to acridone and acridine compounds of formula (I), wherein either: (a) K is ═O, L is —H, alpha is a single bond, beta is a double bond, gamma is a single bond (acridones); or, (b) K is a 9-substituent, L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond (acridines); and wherein: J 1 is a 2- or 3-substituent; J 2 is a 6- or 7-substituent; J 1 and J 2 are each independently a group of the formula —NHCO(CH 2 ) n NR 1 R 2 , wherein: n is an integer from 1 to 5; and, R 1 and R 2 are independently hydrogen, C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl, or R 1 and R 2 , taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 3 to 8 ring atoms; and wherein, when K is a 9-substituent. K is a group of the formula —N(R N )Q, wherein: R N is an amino substituent and is hydrogen, C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl; and, Q is C 1-7 alkyl, C 3-20 heterocyclyl, or (C 5-20 aryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell prol iferation, and in the treatment of proliferative conditions, such as cancer.

  本发明涉及式(I)的吖啶和吖啶类化合物，其中：(a) K为═O，L为—H，α为单键，β为双键，γ为单键（吖啶类）；或者，(b) K为9-取代基，L不存在，α为双键，β为单键，γ为双键（吖啶类）；其中：J1为2-或3-取代基；J2为6-或7-取代基；J1和J2各自独立为式—NHCO(CH2)nNR1R2的基团，其中：n为1到5的整数；R1和R2独立地为氢、C1-7烷基、C3-20杂环烷基或C5-20芳基，或者R1和R2与它们连接的氮原子一起形成具有3到8个环原子的杂环环；当K为9-取代基时，K为式—N(RN)Q的基团，其中：RN为氨基取代基，为氢、C1-7烷基、C3-20杂环烷基或C5-20芳基；Q为C1-7烷基、C3-20杂环烷基或(C5-20芳基，且可选择性取代；以及药学上可接受的盐、酯、酰胺、溶剂化合物、水合物和其保护形式。本发明还涉及包含此类化合物的药物组合物，以及在体内外使用此类化合物和组合物来抑制端粒酶、调节细胞增殖，以及治疗增殖性疾病，如癌症。
• Novel Acridine-Triazenes as Prototype Combilexins: Synthesis, DNA Binding, and Biological Activity
  作者：Adrian W. McConnaughie、Terence C. Jenkins

  DOI：10.1021/jm00018a009

  日期：1995.9

  molecular fragments, have been examined by fluorescence quenching and thermal denaturation studies with calf thymus DNA and two oligonucleotides, [poly(dA-dT)]2 and [poly(dG-dC)]2. In addition, the binding behaviors of these acridine compounds are compared to those of proflavine (3,6-diaminoacridine) and its 9-phenyl derivative. The results indicate that the hybrid agents (i) are more DNA-affinic than either

  使用DNA模板指导的方法已经开发了一系列双功能配体作为结合DNA的原型组合毒素。这些新型药物含有1,3-二芳基三氮烯连接基部分，存在于已建立的DNA小沟黏合剂苯甲腈[1,3-双（4'-ami基苯基）-三氮烯]中，该官能团通过功能化与嵌入的a啶发色团连接噻唑残基。预计该9-芳基吡啶可赋予杂化分子旋转自由度，并因此通过“经典”嵌入和较小的凹槽结合过程的组合促进与双链DNA的双功能相互作用。这些a啶-三氮烯组合毒素与组分分子片段的非共价DNA结合特性 已经通过使用小牛胸腺DNA和两个寡核苷酸[poly（dA-dT）] 2和[poly（dG-dC）] 2的荧光猝灭和热变性研究对它们进行了检查。另外，将这些a啶化合物的结合行为与原黄酮（3，6-二氨基ac啶）及其9-苯基衍生物的结合行为进行了比较。结果表明，杂化剂（i）比任何一种分子组分都具有更高的DNA亲和力，（ii）保留了母体双官能化的1,3-二
• Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19
  作者：Julien Debray、Walid Zeghida、Muriel Jourdan、David Monchaud、Marie-Louise Dheu-Andries、Pascal Dumy、Marie-Paule Teulade-Fichou、Martine Demeunynck

  DOI：10.1039/b912716j

  日期：——

  The present article reports on the design and the synthesis of a series of mono- and bis-pyrimidinoacridines and their evaluation as a novel family of quadruplex-binders. It is shown that bispyrimidinoacridines represent an interesting compromise between easy synthetic access and efficiency in terms of quadruplex interaction (both affinic and selective), as judged by G4-FID assay and molecular modelling. The present study also highlights that control of the π-stacking interactions taking place between the ligand and the accessible G-tetrad of a quadruplex-DNA is indeed essential for good recognition but not exclusively (key role of direct and water-mediated H-bonds). The introduction of additional amino side chains, valuable in the acridine series, results here in steric perturbations of the ligand/quadruplex recognition and lowers the quadruplex/duplex selectivity.

  本文报道了一系列单嘧啶和双嘧啶吖啶的设计和合成，并评估了它们作为新型四联体结合剂的作用。结果表明，根据G4-FID检测和分子建模，双嘧啶吖啶在易于合成和四联体相互作用（亲和力和选择性）效率之间取得了有趣的平衡。本研究还强调，对配体与四联体DNA可及G四联体之间π堆积相互作用的控制对于良好识别确实至关重要，但并非唯一（直接和水介导的氢键的关键作用）。在吖啶系列中引入额外的氨基侧链，会导致配体/四联体识别的空间位阻，并降低四联体/双链的选择性。
• [EN] NOVEL HDMX INHIBITORS AND THEIR USE FOR CANCER TREATMENT<br/>[FR] NOUVEAUX INHIBITEURS HDMX ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：MIRX PHARMACEUTICALS LLC

  公开号：WO2015153535A1

  公开（公告）日：2015-10-08

  The present invention provides for novel acridine-like class of compounds that have demonstrated efficiency in treating cancer. The compounds of the present invention have demonstrated efficacy in binding to and antagonizing the activity of the p53 repressor, HDMX. Once administered to a cell, the compounds of the present invention bind HDMX, thereby allowing p53 to induce apoptosis of the cancerous cell. A combination of this class of compounds along with Nutlin3 provides a novel approach to treat cancers.

  本发明提供了一种新型的类似于吖啶的化合物，已经证明可以有效地治疗癌症。本发明的化合物已经证明在结合并拮抗p53抑制剂HDMX的活性方面具有疗效。一旦这些化合物被注入细胞，它们会与HDMX结合，从而使p53诱导癌细胞凋亡。将这类化合物与Nutlin3结合使用可以提供一种治疗癌症的新方法。