3,6-bis-[3-pyrrolidinopropionamide]-9-acridone | 351351-78-5

• 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: 3,6-bis-[3-pyrrolidinopropionamide]-9-acridone
• 英文别名: 3,6-bis[3-(pyrrolidino)propionamido]-9(10H)-acridone；BRACO-14；N-[9-Oxo-6-(3-pyrrolidin-1-yl-propionylamino)-9,10-dihydro-acridin-3-yl]-3-pyrrolidin-1-yl-propionamide；N-[9-oxo-6-(3-pyrrolidin-1-ylpropanoylamino)-10H-acridin-3-yl]-3-pyrrolidin-1-ylpropanamide
• CAS: 351351-78-5
• 化学式: C₂₇H₃₃N₅O₃
• 分子量: 475.591
• InChiKey: SWVBRNFIKZGFGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  93.8
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,6-bis-[3-pyrrolidinopropionamide]-9-acridone 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 5.0h， 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：

  Trisubstituted Acridine Derivatives as Potent and Selective Telomerase Inhibitors

  摘要：

  The synthesis and evaluation for telomerase-inhibitory and quadruplex DNA binding properties of three related series of rationally designed trisubstituted acridine derivatives are described. These are substituted on the acridine ring at the 2,6,9; 2,7,9; and 3,6,9 positions. The ability of several of the most potent compounds to interact with and stabilize an intramolecular G-quadruplex DNA was evaluated by surface plasmon resonance methods, and affinities were found to correlate with potency in a telomerase assay. The interactions of a number of compounds with a parallel quadruplex DNA structure were simulated by molecular modeling methods. The calculated interaction energies were compared with telomerase activity and showed generally consistent correlations between quadruplex affinity and telomerase inhibition. These data support a model for the action of these compounds that involves the stabilization of intermediate quadruplex structures that inhibit the elongation of telomeric DNA by telomerase in tumor cells.

  DOI：

  10.1021/jm0308693
• 作为产物：
  描述：

  2,2’,4,4’-四硝基二苯甲酮 在 盐酸 、 sodium carbonate 、 tin(ll) chloride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 3,6-bis-[3-pyrrolidinopropionamide]-9-acridone
  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

文献信息

• 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。
• Synthesis and biological evaluation of hybrid acridine-HSP90 ligand conjugates as telomerase inhibitors
  作者：S. Roe、M. Gunaratnam、C. Spiteri、P. Sharma、R. D. Alharthy、S. Neidle、J. E. Moses

  DOI：10.1039/c5ob01177a

  日期：——

  The synthesis and biological evaluation of a series of bifunctional acridine-HSP90 inhibitor ligands as telomerase inhibitors is herein described.

  本文介绍了一系列双功能的吖啶-HSP90抑制剂配体的合成和生物评价，作为端粒酶抑制剂。
• Toward the Design of a Catalytic Metallodrug: Selective Cleavage of G-Quadruplex Telomeric DNA by an Anticancer Copper-Acridine-ATCUN Complex
  作者：Zhen Yu、Menglu Han、James A. Cowan

  DOI：10.1002/anie.201410434

  日期：2015.2.2

  Telomeric DNA represents a novel target for the development of anticancer drugs. By application of a catalytic metallodrug strategy, a copper–acridine–ATCUN complex (CuGGHK‐Acr) has been designed that targets G‐quadruplex telomeric DNA. Both fluorescence solution assays and gel sequencing demonstrate the CuGGHK‐Acr catalyst to selectively bind and cleave the G‐quadruplex telomere sequence. The cleavage

  端粒DNA代表了开发抗癌药物的新靶标。通过应用催化金属药物策略，设计了靶向G-四链体端粒DNA的铜-ac啶-ATCUN复合物（CuGGHK-Acr）。荧光溶液测定和凝胶测序均证明CuGGHK-Acr催化剂可选择性结合并切割G-四链体端粒序列。裂解途径已通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）实验绘制。CuGGHK-Acr可显着抑制癌细胞增殖并缩短端粒长度。在乳腺癌细胞系MCF7中诱导衰老和凋亡。
• Two-in-one: a pH-sensitive, acridine-based, fluorescent probe binds G-quadruplexes in oncogene promoters
  作者：Claudia Percivalle、Tariq Mahmood、Sylvain Ladame

  DOI：10.1039/c2md20173a

  日期：——

  We report the synthesis of an acridine-containing cyanine dye and demonstrate its potential as a pH-responsive colorimetric indicator and fluorescent probe.

  我们报告了一种含有吖啶基的青烷染料的合成，并展示了它作为pH响应性比色指示剂和荧光探针的潜力。
• WO2006/95139
  申请人：——

  公开号：——

  公开（公告）日：——