diethyl {[(2-bromo-5-fluorophenyl)amino]methylene}malonate | 655236-27-4

• 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: diethyl {[(2-bromo-5-fluorophenyl)amino]methylene}malonate
• 英文别名: diethyl 2-(((2-bromo-5-fluorophenyl)amino)methylene)malonate；diethyl {[(2-bromo-5-fluorophenyI)amino]methyIene}malonate；Diethyl 2-[(2-bromo-5-fluoroanilino)methylidene]propanedioate
• CAS: 655236-27-4
• 化学式: C₁₄H₁₅BrFNO₄
• 分子量: 360.18
• InChiKey: KINPNRPJXTVFEX-UHFFFAOYSA-N

物化性质

• 沸点：
  364.9±42.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl {[(2-bromo-5-fluorophenyl)amino]methylene}malonate 在 diphenyl ether-biphenyl eutectic 作用下， 反应 2.0h， 生成 8-溴-5-氟-4-氧代-1H-喹啉-3-羧酸乙酯
  参考文献：
  名称：

  基于喹诺酮支架的 DC-SIGN 类药物抑制剂

  摘要：

  DC-SIGN（树突状细胞特异性细胞间粘附分子-3-抓取非整联蛋白）是一种在免疫细胞上表达的模式识别受体，参与识别各种病原体（包括 HIV、埃博拉病毒和 SARS-CoV）上存在的碳水化合物特征-2。因此，开发阻断 DC-SIGN 碳水化合物结合位点的抑制剂可以产生一种有价值的工具来研究该受体在多种传染病中的作用。在此，我们使用 4-喹诺酮作为支架进行了基于片段的配体设计。我们合成了一个包含 61 种化合物的库，使用 STD 报告基因分析对 DC-SIGN 进行了筛选，并使用基于蛋白质的1 H– 15验证了这些数据NHSQC 核磁共振。基于构效关系数据，我们证明 2 位或 3 位的乙氧基羰基或二甲基氨基羰基有利于 DC-SIGN 结合活性，尤其是与 7 位或 8 位的氟、乙氧基羰基或二甲基氨基羰基组合。此外，我们证明这些喹诺酮类药物可以变构调节碳水化合物结合位点，这为这一具有挑战性的蛋白质靶标提供了另一种方法。

  DOI：

  10.1021/acsmedchemlett.2c00067
• 作为产物：
  描述：

  4-氟-2-硝基苯胺 在 镍 盐酸 、 氢气 、 sodium nitrite 作用下， 反应 16.0h， 生成 diethyl {[(2-bromo-5-fluorophenyl)amino]methylene}malonate
  参考文献：
  名称：

  High affinity central benzodiazepine receptor ligands. Part 3: insights into the pharmacophore and pattern recognition study of intrinsic activities of pyrazolo[4,3- c ]quinolin-3-ones

  摘要：

  Novel 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones (PQs) endowed with high affinity for central benzodiazepine receptor (BzR) were synthesized. In particular, 9-fluoro-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (22) showed binding affinity in the subnanomolar concentration range and proved to be in vitro a potent antagonist. This finding allowed the nature of the hydrogen bonding receptor site H-2 to be established, as located between the N-1 nitrogen of the PQ nucleus and the ortho position of the N-2-aryl group. [S-35]tert-Butylbicyclophosphorothionate ([S-35]TBPS) binding assays and electrophysiological measurements of the effects on GABA-evoked Cl- currents at recombinant human alpha(1)beta(2)gamma(2L) GABA(A) receptors, expressed in Xenopus laevis oocytes, were used to assess the intrinsic activities of a large series of PQs. With the aim of extracting discriminant information and distinguishing BzR ligands with different profiles of efficacy, 51 PQ derivatives, including full and partial agonists, antagonists, and inverse agonists, were analyzed in a multidimensional chemical descriptor space, defined by the lipophilicity parameter CLOG P and 3-D molecular WHIM descriptors, by means of principal component analysis, k-nearest neighbors (k-NN) method, and linear discriminant analysis (LDA). The classification methods were applied to subsets of pairs of efficacy classes, and lipophilicity and 3-D size descriptors were detected as the discriminant variables by a stepwise linear discriminant analysis. LDA proved to be superior to k-NN, especially in classifying PQ ligands (60-84% of success in prediction ability) into categories of efficacies which were contiguous and quite overlapped in the hyperspace of variables. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00527-3

文献信息

• WO2008/2621
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
  作者：Xia Yao、Xiuyun Sun、Shuyu Jin、Ling Yang、Hongjiang Xu、Yu Rao

  DOI：10.1021/acs.jmedchem.9b00329

  日期：2019.7.25

  A structure-hopping strategy was applied to discover a series of novel 4-aminoquinoline-3-carboxamide derivatives as potent, reversible BTK inhibitors. Compared to the previously described cinnoline scaffold compounds, the 4-aminoquinoline analogues showed significantly improved drug-like properties, especially in their aqueous solubility. The most potent compound, 25, displayed a stronger inhibitory effect on both BTKWT (IC50 = 5.3 nM) and BTKC481S (IC50 = 39 nM). In a rodent collagen-induced arthritis model, compound 25 efficiently reduced paw swelling without a loss in body weight. On the basis of potency, drug-like properties, stability, and noncovalent mode of inhibition, our representative inhibitors could have a promising profile to be treatments for a wide range of autoimmune diseases.
• BENZYL-SUBSTITUTED QUINOLONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2037739B1

  公开（公告）日：2011-10-26
• Benzyl-substituted quinolone m1 receptor positive allosteric modulators
  申请人：Lindsley Craig

  公开号：US20100009962A1

  公开（公告）日：2010-01-14

  The present invention is directed to benzyl-substituted quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of diseases in which the M1 receptor is involved.
• US8178667B2
  申请人：——

  公开号：US8178667B2

  公开（公告）日：2012-05-15