6-(Chloromethyl)-2-oxo-2h-1-benzopyran-3-carboxylic acid | 176770-23-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-(Chloromethyl)-2-oxo-2h-1-benzopyran-3-carboxylic acid
• 英文别名: 6-(chloromethyl)-2-oxochromene-3-carboxylic acid
• CAS: 176770-23-3
• 化学式: C₁₁H₇ClO₄
• 分子量: 238.627
• InChiKey: TWIKGUMQJRGZJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(Chloromethyl)-2-oxo-2h-1-benzopyran-3-carboxylic acid 在 吡啶 、 氯化亚砜 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.5h， 生成
  参考文献：
  名称：

  Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket

  摘要：

  The synthesis of novel coumarins bearing on the lateral side chain in the 3-position an amine or a guanidine group is described. In vitro evaluation highlighted 14d which possesses a meta aniline side chain as a very potent THR inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a decrease in THR inhibiting properties. We, thus, used docking experiments to rationalize the SAR in the series. This study showed the crucial role of a conserved water molecule in the specificity pocket of THR during docking simulation in order to explain the inactivity of guanidine derivatives. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.070
• 作为产物：
  描述：

  2-羟基-5-(羟基甲基)苯甲醛 在 哌啶 、 盐酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 20.0h， 生成 6-(Chloromethyl)-2-oxo-2h-1-benzopyran-3-carboxylic acid
  参考文献：
  名称：

  Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket

  摘要：

  The synthesis of novel coumarins bearing on the lateral side chain in the 3-position an amine or a guanidine group is described. In vitro evaluation highlighted 14d which possesses a meta aniline side chain as a very potent THR inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a decrease in THR inhibiting properties. We, thus, used docking experiments to rationalize the SAR in the series. This study showed the crucial role of a conserved water molecule in the specificity pocket of THR during docking simulation in order to explain the inactivity of guanidine derivatives. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.070

文献信息

• Esters and Amides of 6-(Chloromethyl)-2-oxo-2<i>H</i>-1-benzopyran-3-carboxylic Acid as Inhibitors of α-Chymotrypsin:  Significance of the “Aromatic” Nature of the Novel Ester-Type Coumarin for Strong Inhibitory Activity
  作者：Lionel Pochet、Caroline Doucet、Marc Schynts、Nicole Thierry、Nicole Boggetto、Bernard Pirotte、Kai Y. Jiang、Bernard Masereel、Pascal de Tullio、Jacques Delarge、Michèle Reboud-Ravaux

  DOI：10.1021/jm960090b

  日期：1996.1.1

  activity toward bovine alpha-chymotrypsin and human leukocyte elastase. Both series behaved as time-dependent inhibitors of alpha-chymotrypsin, but ester-type coumarins were clearly more efficient than the corresponding amides in inactivating the serine proteinase. The best inactivations were observed with "aromatic" esters, in particular with meta-substituted phenyl esters such as m-chlorophenyl 6-(chlor

  合成了一系列6-（氯甲基）-2-氧代-2H-1-苯并吡喃-3-羧酸的酯和酰胺，并在体外评估了它们对牛α-胰凝乳蛋白酶和人白细胞弹性蛋白酶的抑制活性。这两个系列均表现为α-胰凝乳蛋白酶的时间依赖性抑制剂，但酯型香豆素在灭活丝氨酸蛋白酶方面显然比相应的酰胺更有效。用“芳族”酯，尤其是间位取代的苯基酯，例如间氯苯基6-（氯甲基）-2-氧代-2H-1-苯并吡喃-3-羧酸酯，观察到最好的灭活。最强大的α-胰凝乳蛋白酶灭活剂（在pH 7.5和25摄氏度下，激酶/ KI = 760,000 M-1 S-1）的报道。通常，香豆素衍生物不能显着抑制人白细胞弹性蛋白酶。
• DERIVES DE COUMARINES, LEURS PROCEDES DE PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS
  申请人：CENTRE NATIONAL DELA RECHERCHE SCIENTIFIQUE

  公开号：EP0988298A1

  公开（公告）日：2000-03-29
• US6355658B1
  申请人：——

  公开号：US6355658B1

  公开（公告）日：2002-03-12
• [EN] COUMARIN DERIVATIVES, METHODS OF PREPARATION AND APPLICATION AS MEDICINES<br/>[FR] DERIVES DE COUMARINES, LEURS PROCEDES DE PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：WO1998055472A1

  公开（公告）日：1998-12-10

  (EN) The invention concerns compounds of general formula (I) in which: X, X' and X'' independently of each other represent O or S; Y represents O, S, NH or NHS; R3 represents in particular a cycloalkyl group; R5, R6, R7 and R8 mutually identical or different, represent in particular hydrogen; a halogen atom. Said compounds can be used as active substances of medicines as inhibitors of protease.(FR) L'invention a pour objet des composés répondant à la formule générale (I) dans laquelle X, X' et X'' représentent indépendamment l'un de l'autre O ou S, Y représente O, S, NH ou NHS, R3 représente notamment un groupe cycloalkyle, R5, R6, R7 et R8 identiques ou différents entre eux, représentent notamment l'hydrogène; un atome d'halogène. Ces composés peuvent être utilisés comme substances actives de médicaments en tant qu'inhibiteurs de protéases.
• Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket
  作者：Raphaël Frédérick、Caroline Charlier、Séverine Robert、Johan Wouters、Bernard Masereel、Lionel Pochet

  DOI：10.1016/j.bmcl.2005.12.070

  日期：2006.4

  The synthesis of novel coumarins bearing on the lateral side chain in the 3-position an amine or a guanidine group is described. In vitro evaluation highlighted 14d which possesses a meta aniline side chain as a very potent THR inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a decrease in THR inhibiting properties. We, thus, used docking experiments to rationalize the SAR in the series. This study showed the crucial role of a conserved water molecule in the specificity pocket of THR during docking simulation in order to explain the inactivity of guanidine derivatives. (C) 2006 Elsevier Ltd. All rights reserved.