3-methoxy-5-carboxy-9(10H)-acridanone | 86611-40-7

• 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: 3-methoxy-5-carboxy-9(10H)-acridanone
• 英文别名: 6-methoxy-9-oxo-10H-acridine-4-carboxylic acid
• CAS: 86611-40-7
• 化学式: C₁₅H₁₁NO₄
• 分子量: 269.257
• InChiKey: AIXDWBWBHAFINF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-methoxy-5-carboxy-9(10H)-acridanone 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 9-Chloro-6-methoxy-acridine-4-carboxylic acid methylamide
  参考文献：
  名称：

  Potential antitumor agents. Part 38. 3-Substituted 5-carboxamido derivatives of amsacrine

  摘要：

  The synthesis and biological evaluation of a series of 3-substituted 5-carboxamido derivatives of amsacrine (m-AMSA) are described. This series was developed as the result of previous quantitative structure-activity relationship (QSAR) studies of the antitumor activity of 9-anilinoacridine derivatives. In agreement with these studies, this class of compounds, possessing a variety of small nonpolar groups at the 3-position, together with very hydrophilic carboxamido groups at the 5-position, have high in vivo activity against animal leukemia models.

  DOI：

  10.1021/jm00365a013
• 作为产物：
  描述：

  2,6-二羧基苯胺 在 copper(l) chloride N-乙基吗啉 、 PPA 作用下， 以 苯 为溶剂， 反应 3.0h， 生成 3-methoxy-5-carboxy-9(10H)-acridanone
  参考文献：
  名称：

  The Synthesis of Substituted 9-Oxoacridan-4-carboxylic Acids; Part 2. The Use of 2-lodoisophthalic Acid in the Jourdan-Ullmann Reaction

  摘要：

  DOI：

  10.1055/s-1985-31164

文献信息

• Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2
  作者：Ahcene Boumendjel、Sira Macalou、Abdelhakim Ahmed-Belkacem、Madeleine Blanc、Attilio Di Pietro

  DOI：10.1016/j.bmc.2007.02.017

  日期：2007.4

  The breast cancer resistance protein (BCRP, ABCG2) is among the latest discovered ABC proteins to be involved in MDR phenotype and for which only few inhibitors are known. In continuing our program aimed at discovering efficient multidrug resistance modulators, we conceived and synthesized new acridones as ABCG2 inhibitors. The design of target molecules was based on earlier results dealing with ABCG2

  乳腺癌抗性蛋白（BCRP，ABCG2）是与MDR表型有关的最新发现的ABC蛋白之一，而对于它的抑制剂却鲜为人知。在继续我们旨在发现有效的多药耐药性调节剂的计划时，我们构思并合成了新的cri啶酮作为ABCG2抑制剂。靶分子的设计是基于较早的有关黄酮和色酮衍生物对ABCG2抑制作用的结果。将人类野生型（R482）ABCG2转染的细胞用于合理筛选抑制性cri烯。描述了目标化合物的合成，对ABCG2的抑制活性以及构效关系。正如其抑制米托蒽醌外排的能力所示，其中一种a啶酮甚至比参考抑制剂GF120918更有效。
• Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide
  作者：Graham J. Atwell、Gordon W. Rewcastle、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00387a014

  日期：1987.4

  antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor

  报道了一系列N- [2-（二烷基氨基）烷基] ac啶-4-羧酰胺的合成，理化性质和抗肿瘤活性。这些化合物通过插层与DNA结合，但由于弱碱性a啶发色团（pKa = 3.5-4.5）而在生理条件下以单阳离子形式存在。an啶-4-甲酰胺显示出非常广泛的抗白血病活性的结构-活性关系（SAR），几乎所有all啶位置上的取代基都被证明是可以接受的。所述化合物还具有体内抗路易斯肺实体瘤的显着活性，其几种类似物能够100％治愈晚期疾病。9-ac啶-4-羧酰胺具有宽泛的SAR和较高的固体肿瘤活性，这意味着它们应被视为一类全新的抗肿瘤药物。
• Stewart, Georgina M.; Rewcastle, Gordon W.; Denny, William A., Australian Journal of Chemistry, 1984, vol. 37, # 9, p. 1939 - 1950
  作者：Stewart, Georgina M.、Rewcastle, Gordon W.、Denny, William A.

  DOI：——

  日期：——
• Rewcastle, Gordon W.; Denny, William A, Synthetic Communications, 1987, vol. 17, # 3, p. 309 - 318
  作者：Rewcastle, Gordon W.、Denny, William A

  DOI：——

  日期：——
• Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide
  作者：Gordon W. Rewcastle、Graham J. Atwell、David Chambers、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00154a008

  日期：1986.4

  A series of monosubstituted derivatives of the new antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide has been prepared, bearing methyl, methoxy, and chloro groups at available acridine positions. The physicochemical properties and antitumor activity of these compounds varied more with the position than with the nature of the substituent groups. The highest levels of both in vitro and in vivo antileukemic activity were shown by 5-substituted derivatives, while 7- and 8-substituted derivatives possessed the highest selectivity toward the HCT-8 human colon carcinoma line compared to the L1210 mouse leukemia line in vitro.