2-[2-(2,4-dichlorophenoxy)acetylamino]benzoic acid methyl ester

• 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-(2,4-dichlorophenoxy)acetylamino]benzoic acid methyl ester
• 英文别名: 2-[2-(2,4-dichloro-phenoxy)-acetylamino]-benzoic acid methyl ester；Methyl 2-{[(2,4-dichlorophenoxy)acetyl]amino}benzoate；methyl 2-[[2-(2,4-dichlorophenoxy)acetyl]amino]benzoate
• 化学式: C₁₆H₁₃Cl₂NO₄
• mdl: MFCD00100452
• 分子量: 354.19
• InChiKey: RMRKNLVWWHUNLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[2-(2,4-dichlorophenoxy)acetylamino]benzoic acid methyl ester 在 potassium carbonate 、 一水合肼 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 丙酮 、 正丁醇 、 苯 为溶剂， 反应 55.5h， 生成 2-[(6-(4-chlorophenyl)-5-cyano-4-(4-hydroxyphenylamino)pyrimidin-2-yl)sulfanyl]-N-[2-(2,4-dichlorophenoxymethyl)-4-oxo-4H-quinazolin-3-yl]acetamide
  参考文献：
  名称：

  New quinazolinone–pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies

  摘要：

  Two groups of hybrid compounds: the quinazolinone dihydropyrimidines and quinazolinone pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC50 = 116.73 mu mol/kg; ulcer index = 11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.050
• 作为产物：
  描述：

  2,4-二氯苯氧乙酸 、 邻氨基苯甲酸甲酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以66.6%的产率得到2-[2-(2,4-dichlorophenoxy)acetylamino]benzoic acid methyl ester
  参考文献：
  名称：

  苯氧基-N-苯乙酰胺衍生物作为新型 P-糖蛋白抑制剂的合成和生物学评价

  摘要：

  P-糖蛋白 (Pgp) 的过表达与肿瘤细胞对多种化疗药物的多药耐药性 (MDR) 相关。Pgp 抑制剂已被证明可有效逆转 Pgp 介导的 MDR。我们制备了一系列苯氧基-N-苯基乙酰胺衍生物，并使用过表达 Pgp 的 MCF-7/ADR 细胞系测试了它们作为潜在的 MDR 逆转剂抑制 Pgp 的能力。一些合成的化合物表现出中等至强效的逆转活性。值得注意的是，与众所周知的 Pgp 抑制剂维拉帕米相比，化合物 4o 的抑制作用增加了 3.0 倍。此外，代表性化合物 4o 和底物抗癌剂阿霉素的共同处理导致阿霉素的抗肿瘤作用显着增加，并抑制 MCF-7/ADR 细胞系中的 DNA 合成。综合起来，

  DOI：

  10.5012/bkcs.2011.32.10.3666

文献信息

• COMPOUNDS THAT INHIBIT HIF-1 ACTIVITY, THE METHOD FOR PREPARATION THEREOF AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM AS AN EFFECTIVE COMPONENT
  申请人：Lee Jung Joon

  公开号：US20090306078A1

  公开（公告）日：2009-12-10

  Disclosed herein are an HIF-1 inhibitor, a method for the preparation thereof, and a pharmaceutical composition comprising the same as an active ingredient. The HIF-1 inhibitor shows anticancer activity thanks to the inhibition activity against HIF-1, a transcription factor which plays an important role in the growth and metastasis of cancer, but not to general cytotoxicity. Thus, the HIF-inhibitor and a pharmaceutically acceptable salt thereof can be used as a therapeutic for various cancers such as liver cancer; stomach cancer and breast cancer. Also, the compound having inhibition activity against HIF-1 is useful in the treatment of diabetic retinopathy and arthritis, which are aggravated by HIF-1-mediated VEGF expression.

  本文披露了一种HIF-1抑制剂，其制备方法，以及包含其作为活性成分的药物组合物。该HIF-1抑制剂显示抗癌活性，这归功于其对HIF-1的抑制活性，HIF-1是一种在癌症生长和转移中起重要作用的转录因子，但不具有一般细胞毒性。因此，HIF抑制剂及其药用可接受的盐可用作治疗各种癌症，如肝癌、胃癌和乳腺癌的治疗药物。此外，具有对HIF-1抑制活性的化合物在治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎方面是有用的。
• Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H)-one Derivatives
  作者：Hanan Georgey、Nagwa Abdel-Gawad、Safinaz Abbas

  DOI：10.3390/molecules13102557

  日期：——

  ) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds

  已经合成了许多3-取代的-2-（取代的苯氧基甲基）喹唑啉-4（3H）-一衍生物4a，b，5a-c，6，7a-f，8a-e和9a，b。在元素分析和光谱研究（IR，1H-NMR，MS）的基础上阐明了它们的结构。对制备的化合物的抗惊厥活性的初步评估表明，化合物4b，7b-f，8a和9b表现出显着的抗惊厥活性，而化合物6、8b和8d表现出轻度至中度活性。
• Design and Synthesis of Some 3-Substituted-2-[(2,4-dichlorophenoxy)-methyl]quinazolin-4(3<i>H</i>)-one Derivatives as Potential Anticonvulsant Agents
  作者：Safinaz El-Sayed Abbas、Fadi Mohsen Awadallah、Nashwa Ahmed Ibrahim、Eman Gaber Said、Gihan Kamel

  DOI：10.1248/cpb.c12-01064

  日期：——

  Series of 2,3-disubstituted quinazolinone derivatives and a [1,2,4]triazino[2,3-c]quinazolinone featuring the pharmacophoric elements of anticonvulsant drugs were designed and synthesized. Target compounds were screened for their anticonvulsant activity using the subcutaneous pentylenetetrazole (s.c. PTZ) and maximal electroshock (MES) models. The s.c. PTZ test showed that the most active compound

  设计并合成了具有抗惊厥药药理学特征的2,3-二取代喹唑啉酮衍生物和[1,2,4]三嗪基[2,3-c]喹唑啉酮系列。使用皮下戊四氮（sc PTZ）和最大电击（MES）模型筛选目标化合物的抗惊厥活性。sc PTZ测试表明，活性最高的化合物是酰胺衍生物9c，其保护剂量50（PD50）为200.53 µmol / kg（苯巴比妥酮的PD50 = 62.18 µmol / kg）；但是，这种低效价却远远超过了9c的更高安全性（LD50> 3000 mg / kg）。在MES筛选中，有7种化合物的活性等于或高于苯妥英。其中一些化合物的神经毒性低于苯妥英钠。在这两个模型中，很少有化合物（例如9c和10）有效。
• Compounds that inhibit HIF-1 activity, the method for preparation thereof and the pharmaceutical composition containing them as an effective component
  申请人：Lee Jung Joon

  公开号：US08394799B2

  公开（公告）日：2013-03-12

  Disclosed herein are an HIF-1 inhibitor, a method for the preparation thereof, and a pharmaceutical composition comprising the same as an active ingredient. The HIF-1 inhibitor shows anticancer activity thanks to the inhibition activity against HIF-1, a transcription factor which plays an important role in the growth and metastasis of cancer, but not to general cytotoxicity. Thus, the HIF-inhibitor and a pharmaceutically acceptable salt thereof can be used as a therapeutic for various cancers such as liver cancer; stomach cancer and breast cancer. Also, the compound having inhibition activity against HIF-1 is useful in the treatment of diabetic retinopathy and arthritis, which are aggravated by HIF-1-mediated VEGF expression.

  本发明涉及一种HIF-1抑制剂，其制备方法以及包含该抑制剂作为活性成分的制药组合物。该HIF-1抑制剂通过对HIF-1的抑制活性表现出抗癌活性，HIF-1是一种转录因子，在癌症的生长和转移中起着重要作用，但不具有普遍的细胞毒性。因此，HIF抑制剂及其药学上可接受的盐可以用作各种癌症（如肝癌、胃癌和乳腺癌）的治疗剂。此外，具有对HIF-1抑制活性的化合物对于治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎非常有用。
• WO2008/4798
  申请人：——

  公开号：——

  公开（公告）日：——