4-bromo-5-ethoxy-3-hydroxybenzoic acid | 149517-93-1

• 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: 4-bromo-5-ethoxy-3-hydroxybenzoic acid
• 英文别名: 4-bromo-3-ethoxy-5-hydroxybenzoic acid
• CAS: 149517-93-1
• 化学式: C₉H₉BrO₄
• 分子量: 261.072
• InChiKey: YMFQGIGHFCPKEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-5-ethoxy-3-hydroxybenzoic acid 在 N-乙基吗啉 、 盐酸 、 sodium hydroxide 、 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 PPh₃-polystyrene 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-Bromo-3-[2-(2,4-Dichloro-Phenyl)-Ethoxy]-5-Ethoxy-N-(3,4,5,6-Tetrahydro-2H-[1,4']Bipyridinyl-4-Ylmethyl)-Benzamide
  参考文献：
  名称：

  Structural Requirements for Factor Xa Inhibition by 3-Oxybenzamides with Neutral P1 Substituents:  Combining X-ray Crystallography, 3D-QSAR, and Tailored Scoring Functions

  摘要：

  The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.

  DOI：

  10.1021/jm049187l
• 作为产物：
  描述：

  4-溴-3,5-二乙氧基苯甲酸乙酯 在 乙硫醇钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以14%的产率得到4-bromo-5-ethoxy-3-hydroxybenzoic acid
  参考文献：
  名称：

  Synthesis and QSAR of substituted 3-hydroxyanthranilic acid derivatives as inhibitors of 3-hydroxyanthranilic acid dioxygenase (3-HAO)

  摘要：

  DOI：

  10.1016/s0223-5234(99)00220-2

文献信息

• 3-Hydroxy anthranilic acid derivatives for inhibiting 3-hydroxy anthranilate oxygenase
  申请人：Astra Aktiebolag

  公开号：EP0530166A2

  公开（公告）日：1993-03-03

  The present invention relates to novel derivatives of 3-hydroxyanthranilic acid of the general formula I, methods for their preparation, novel pharmaceutical compositions and the use thereof for inhibiting the emzyne 3-hydroxyanthranilate oxygenase, 3-HAO, responsible for the production of the endogenous neurotoxin quinolinic acid, QUIN.

  本发明涉及一般式I的3-羟基蒽醌酸的新颖衍生物，其制备方法，新型药物组合物以及用于抑制产生内源神经毒素喹啉酸QUIN的酶3-羟基蒽醌酸氧化酶3-HAO的用途。
• NEW COMPOUNDS
  申请人：Astra Aktiebolag

  公开号：EP0643686A1

  公开（公告）日：1995-03-22
• [EN] NEW COMPOUNDS
  申请人：AB ASTRA

  公开号：WO1993005012A1

  公开（公告）日：1993-03-18

  (EN) The present invention relates to novel derivatives of 3-hydroxyanthranilic acid of general formula (I), methods for their preparation, novel pharmaceutical compositions and the use thereof for inhibiting the enzyme 3-hydroxyanthranilate oxygenase, 3-HAO, responsible for the production of the endogenous neurotoxin quinolinic acid, QUIN.(FR) L'invention a trait à de nouveaux dérivés de l'acide 3-hydroxyanthranilique de formule générale (I), à leurs procédés de préparation, à de nouvelles compositions pharmaceutiques et à leurs utilisations pour inhiber l'enzyme 3-hydroxyanthranilate oxygénase, 3-HAO, responsable de la production d'une neurotoxine endogène, l'acide quinolinique, QUIN.