2-((2-carboxy-5-chlorophenyl)amino)-3-methoxybenzoic acid | 1300731-90-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((2-carboxy-5-chlorophenyl)amino)-3-methoxybenzoic acid
• 英文别名: 2-(2-Carboxy-5-chloroanilino)-3-methoxybenzoic acid
• CAS: 1300731-90-1
• 化学式: C₁₅H₁₂ClNO₅
• 分子量: 321.717
• InChiKey: POYJXSRFNSRIGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.49
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  95.86
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-((2-carboxy-5-chlorophenyl)amino)-3-methoxybenzoic acid 在 硫酸 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 1-chloro-N-(3-(dimethylamino)butyl)-5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxamide
  参考文献：
  名称：

  一种氮杂芳环烷基氨基吖啶酮-4-酰胺类化合物 及其制备方法与应用

  摘要：

  本发明提供一种式I或式II所示的氮杂芳环烷基氨基吖啶酮-4-酰胺类化合物及其制备方法与应用。式I、式II中，R1为H、OCH3、OCH2CH3、OCH2CH2CH3、Cl、Br、CF3、NO2或碳原子数为1-5的直链烷基，R2为N(CH3)2或OCH3，R3为2-吡啶基、3-吡啶基、4-吡啶基、吲哚基、喹啉基、嘧啶基或吡嗪基，m＝1，2，3或4，n＝1，2，3或4。经过多种肿瘤细胞系测试(包括肝癌细胞，白血病细胞等)以及DNA连接，拓扑异构酶测试，证明本发明的化合物是一种潜在的具有DNA连接以及对拓扑异构酶有抑制活性的抗肿瘤药物。本发明提供的化合物原料易得，制备方法简单，实验证明其有良好的抗癌效果，在抗肿瘤药物设计研发领域有着良好的应用前景。

  公开号：

  CN104262327B
• 作为产物：
  描述：

  2-氨基-3-甲氧基苯甲酸 、 2-溴-4-氯苯甲酸 在 铜 、 potassium carbonate 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 2.5h， 以92%的产率得到2-((2-carboxy-5-chlorophenyl)amino)-3-methoxybenzoic acid
  参考文献：
  名称：

  Radiosynthesis and in vivo evaluation of 1-[18F]fluoroelacridar as a positron emission tomography tracer for P-glycoprotein and breast cancer resistance protein

  摘要：

  Aim of this study was to label the potent dual P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) inhibitor elacridar (1) with F-18 to provide a positron emission tomography (PET) radiotracer to visualize Pgp and BCRP. A series of new 1- and 2-halogen- and nitro-substituted derivatives of 1 (4a-e) was synthesized as precursor molecules and reference compounds for radiolabelling and shown to display comparable in vitro potency to 1 in increasing rhodamine 123 accumulation in a cell line overexpressing human Pgp (MDCKII-MDR1). 1-[F-18]fluoroelacridar ([F-18]4b) was synthesized in a decay-corrected radiochemical yield of 1.7 +/- 0.9% by a 1-step no-carrier added nucleophilic aromatic F-18-substitution of 1-nitro precursor 4c. Small-animal PET imaging of [F-18]4b was performed in naive rats, before and after administration of unlabelled 1 (5 mg/kg, n = 3), as well as in wild-type and Mdr1a/b((-/-)) Bcrp1((-/-)) mice (n = 3). In PET experiments in rats, administration of unlabelled 1 increased brain activity uptake by a factor of 9.5 (p = 0.0002, 2-tailed Student's t-test), whereas blood activity levels remained unchanged. In Mdr1a/b((-/-)) Bcrp1((-/-)) mice, the mean brain-to-blood ratio of activity at 60 min after tracer injection was 7.6 times higher as compared to wild-type animals (p = 0.0002). HPLC analysis of rat brain tissue extracts collected at 40 min after injection of [F-18]4b revealed that 93 +/- 7% of total radioactivity in brain was in the form of unchanged [F-18] 4b. In conclusion, the in vivo behavior of [F-18]4b was found to be similar to previously described [C-11]1 suggesting transport of [F-18]4b by Pgp and/or BCRP at the rodent BBB. However, low radiochemical yields and a significant degree of in vivo defluorination will limit the utility of [F-18]4b as a PET tracer. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.039

文献信息

• Novel multi-substituted benzyl acridone derivatives as survivin inhibitors for hepatocellular carcinoma treatment
  作者：Bin Zhang、Ning Wang、Cunlong Zhang、Chunmei Gao、Wei Zhang、Kang Chen、Weibin Wu、Yuzong Chen、Chunyan Tan、Feng Liu、Yuyang Jiang

  DOI：10.1016/j.ejmech.2017.02.027

  日期：2017.3

  HCC cells with high survivin expression, however, the antitumor activity needs to be further improved. Based on molecular docking and rational design method, a series of multi-substituted benzyl acridone derivatives were designed and synthesized. MTT assay indicated that some of the synthesized compounds displayed better antiproliferative activity against HepG2 cells than YM155. Later study indicated

  索拉非尼是FDA批准用于治疗晚期肝细胞癌（HCC）的唯一小分子药物。最近的研究表明，YM155是具有高存活蛋白表达的HCC细胞的有前途的药物，但是其抗肿瘤活性需要进一步提高。基于分子对接和合理的设计方法，设计合成了一系列多取代的苄基a啶酮衍生物。MTT分析表明，某些合成的化合物对HepG2细胞显示出比YM155更好的抗增殖活性。后来的研究表明，代表性化合物8u可能与survivin蛋白直接相互作用，并诱导HepG2细胞凋亡，这与YM155不同。此外，ADME特性在计算机上得到了预测，并且表现良好。而且，
• 多取代苯基烷氨基吖啶酮-4-酰胺类化合物及 其制备方法和用途
  申请人：清华大学深圳研究生院

  公开号：CN105693609B

  公开（公告）日：2019-03-05

  本发明提供了多取代苯基烷氨基吖啶酮‑4‑酰胺类化合物及其制备方法和用途，其中，该化合物为具有式I所示结构式的多取代苯基烷氨基吖啶酮‑4‑酰胺类化合物或其药学上可接受的盐、酯或溶剂合物，其中，R1、R2、R3和n如说明书中定义。本发明的该化合物能够有效抑制肿瘤细胞内Survivin蛋白的表达、抑制DNA拓扑异构酶的活性、抑制真核生物肿瘤细胞增殖、预防和/或治疗肿瘤。
• Molecular design, synthesis and biological research of novel pyridyl acridones as potent DNA-binding and apoptosis-inducing agents
  作者：Bin Zhang、Kang Chen、Ning Wang、Chunmei Gao、Qinsheng Sun、Lulu Li、Yuzong Chen、Chunyan Tan、Hongxia Liu、Yuyang Jiang

  DOI：10.1016/j.ejmech.2015.02.003

  日期：2015.3

  A series of novel pyridyl acridone derivatives comprised of a pseudo-five-cyclic system to extend the pi-conjugated acridone chromophore, were designed and synthesized as potent DNA binding antitumor compounds. Most synthesized compounds displayed good activity against human leukemia K562 cells in MU tests, with compound 6d exhibiting the highest activity with IC50 value at 0.46 mu M. Moreover, 6d showed potent activities against solid tumor cell lines (0.16-3.79 mu M). Several experimental studies demonstrated that the antitumor mode of action of compound 6d involves DNA intercalation, topoisomerase I inhibition, and apoptosis induction through the mitochondrial pathway. In summary, compound 6d represents a novel and promising lead structure for the development of new potent anticancer DNA-binding agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Discovery of novel polysubstituted <i>N</i> -alkyl acridone analogues as histone deacetylase isoform-selective inhibitors for cancer therapy
  作者：Ze Wang、Li Zhao、Bo Zhang、Jiahe Feng、Yule Wang、Bin Zhang、Haixiao Jin、Lijian Ding、Ning Wang、Shan He

  DOI：10.1080/14756366.2023.2206581

  日期：2023.12.31
• CN115557890
  申请人：——

  公开号：——

  公开（公告）日：——