2,7-bis(3-chloropropionamido)-9(10H)-acridone | 393570-59-7

• 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: 2,7-bis(3-chloropropionamido)-9(10H)-acridone
• 英文别名: 3-chloro-N-[7-(3-chloropropanoylamino)-9-oxo-10H-acridin-2-yl]propanamide
• CAS: 393570-59-7
• 化学式: C₁₉H₁₇Cl₂N₃O₃
• 分子量: 406.268
• InChiKey: APRKPXLVYJNECM-UHFFFAOYSA-N

物化性质

• 沸点：
  718.7±60.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,7-bis(3-chloropropionamido)-9(10H)-acridone 、 2-哌啶甲醇 以to give the desired product JM-ACO-11 (888 mg, 63%) as a pale yellow/green solid的产率得到2,7-bis[3-(2-hydroxymethylpiperidino)propionamido]-9(10H)-acridone
  参考文献：
  名称：

  Therapeutic acridone and acridine compounds

  摘要：

  本发明涉及公式（I）的乙酰吖啶和吖啶化合物，其中：（a）K为═O，L为—H，alpha为单键，beta为双键，gamma为单键（乙酰吖啶）；或者，（b）K为9-取代基，L不存在，alpha为双键，beta为单键，gamma为双键（吖啶）；其中：J1为2-或3-取代基；J2为6-或7-取代基；J1和J2各自独立为公式—NHCO（CH2）nNR1R2的基团，其中：n为1至5的整数；R1和R2独立地为氢、C1-7烷基、C3-20杂环基或C5-20芳基，或R1和R2与它们所连接的氮原子形成具有3至8个环原子的杂环环；当K为9-取代基时，K为公式—N（RN）Q的基团，其中：RN为氨基取代基，且为氢、C1-7烷基、C3-20杂环基或C5-20芳基；Q为C1-7烷基、C3-20杂环基或C5-20芳基，且可以被取代；以及其药学上可接受的盐、酯、酰胺、溶剂化合物、水合物和保护形式。本发明还涉及包含这种化合物的制药组合物，以及这种化合物和组合物的使用，无论是体外还是体内，用于抑制端粒酶、调节细胞增殖，并用于治疗增殖性疾病，如癌症。

  公开号：

  US07300930B2
• 作为产物：
  描述：

  二苯基甲烷 在 氯化亚砜 、 硫酸 、 potassium nitrate 作用下， 反应 11.67h， 生成 2,7-bis(3-chloropropionamido)-9(10H)-acridone
  参考文献：
  名称：

  含硼吖啶衍生物、其制备方法和应用

  摘要：

  本发明公开了一种含硼吖啶衍生物，通式为，本发明采用对端粒酶有抑制作用的吖啶衍生物作为硼载体，来提高对肿瘤的选择性，同时该类化合物对多种肿瘤都可能有效，从而实现硼载体的高选择性和广谱性，进一步推动BNCT的发展。

  公开号：

  CN104151339B

文献信息

• Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding
  作者：R. John Harrison、Anthony P. Reszka、Shozeb M. Haider、Barbara Romagnoli、James Morrell、Martin A. Read、Sharon M. Gowan、Christopher M. Incles、Lloyd R. Kelland、Stephen Neidle

  DOI：10.1016/j.bmcl.2004.09.037

  日期：2004.12

  The synthesis and evaluation of a group of 2,6-, 2,7- and 3,6-bis-aminoalkylamido acridones are reported, which show a similar level of activity against telomerase in vitro compared to their acridine counterparts. Computer modelling and calculations of relative binding energies suggest an equivalent binding mode to human intramolecular G-quadruplex DNA, but with significantly reduced affinity; as a result of the limited delocalisation of the acridone chromophore compared to the acridine system. Thermal melting studies on acridone and acridine quadruplex complexes using a FRET approach support these predictions. Long-term cell proliferation studies at sub-cytotoxic doses with two representative acridones using the SKOV3 cell line, show that neither compound produces growth arrest, in contrast with the effects produced by the tri-substituted acridine compound BRACO-19. It is concluded that telomerase inhibitory activity is a necessary though by itself insufficient property in order for cellular growth arrest to occur at sub-toxic concentrations, and that tight quadruplex binding is also required. (C) 2004 Elsevier Ltd. All rights reserved.
• THERAPEUTIC ACRIDONE AND ACRIDINE COMPOUNDS
  申请人：Cancer Research Technology Limited

  公开号：EP1363888A2

  公开（公告）日：2003-11-26
• US7160896B2
  申请人：——

  公开号：US7160896B2

  公开（公告）日：2007-01-09
• US7300930B2
  申请人：——

  公开号：US7300930B2

  公开（公告）日：2007-11-27
• [EN] THERAPEUTIC ACRIDONE AND ACRIDINE COMPOUNDS<br/>[FR] COMPOSES THERAPEUTIQUES D'ACRIDONE ET D'ACRIDINE
  申请人：CANCER RES VENTURES LTD

  公开号：WO2002008193A2

  公开（公告）日：2002-01-31

  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: J1 is a 2- or 3-substituent; J2 is a 6- or 7-substituent; J?1 and J2¿ are each independently a group of the formula -NHCO(CH¿2?)nNR?1R2¿, wherein: n is an integer from 1 to 5; and, R?1 and R2¿ are independently hydrogen, C¿1-7?alkyl, C3-20heterocyclyl, or C5-20aryl, or R?1 and R2¿, 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(RN)Q, wherein: RN is an amino substituent and is hydrogen, C¿1-7?alkyl, C3-20heterocyclyl, or C5-20aryl; and, Q is C1-7alkyl, C3-20heterocyclyl, or C5-20aryl, 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.