6-hydroxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester | 176770-20-0

• 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-hydroxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester
• 英文别名: ethyl 6-(hydroxymethyl)-2-oxo-2H-1-benzopyran-3-carboxylate；6-hydroxymethyl-2-oxo-2H-chromene-3-carboxylic acid ethyl ester；6-Hydroxymethyl-2-oxo-2H-chromen-3-carbonsaeure-aethylester；ethyl 6-(hydroxymethyl)-2-oxo-2H-chromene-3-carboxylate；ethyl 6-(hydroxymethyl)-2-oxochromene-3-carboxylate
• CAS: 176770-20-0
• 化学式: C₁₃H₁₂O₅
• 分子量: 248.235
• InChiKey: LJKJRALGZCZICN-UHFFFAOYSA-N

物化性质

• 熔点：
  109-110 °C
• 沸点：
  464.8±45.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2932209090

反应信息

• 作为反应物：
  描述：

  6-hydroxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester 在 吡啶 、 盐酸 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 7.5h， 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：

  邻甲基苄醇 在 哌啶 、 盐酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 17.33h， 生成 6-hydroxymethyl-2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester
  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。
• Coumarin derivatives, methods of preparation and application as medicines
  申请人：Centre National de la Recherche Scientifique

  公开号：US06355658B1

  公开（公告）日：2002-03-12

  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.

  该发明涉及一般式（I）的化合物，其中：X，X'和X''分别表示O或S; Y表示O，S，NH或NHS; R3特别表示环烷基; R5，R6，R7和R8相互相同或不同，特别表示氢;卤素原子。这些化合物可用作药物的活性物质，作为蛋白酶抑制剂。
• 3,6-Disubstituted Coumarins as Mechanism-Based Inhibitors of Thrombin and Factor Xa
  作者：Raphaël Frédérick、Séverine Robert、Caroline Charlier、Jérôme de Ruyck、Johan Wouters、Bernard Pirotte、Bernard Masereel、Lionel Pochet

  DOI：10.1021/jm050448g

  日期：2005.12.1

  In this work, coumarins were screened on thrombin (THR) and factor Xa (FXa), two of the most promising targets for the development of anticoagulant drugs. This allowed us to highlight compound 30, characterized by a 2,5-dichlorophenyl ester in the 3-position and a chloromethyl moiety in the 6-position, as a very potent THR inhibitor (k(i)/K-I, = 37 000 M-1 s(-1)). Moreover, this compound exhibits good selectivity over FXa (168-fold) and trypsin (54-fold). The mechanism of inactivation was investigated in this series and significantly differs from that previously observed with (x-chymotrypsin. Indeed, the addition of hydrazine on the THR-inhibitor complex promotes a partial induced THR reactivation. This reactivation, confirmed by LC/MS, showed the resurgence of the native THR and a new dihydrazide complex. Docking experiments were then efficiently used to explain the trends observed in the enzymatic assays as well as to corroborate the postulated inhibition mechanism. Finally, the cell permeability of our derivatives was estimated using a computational approach.
• Über den 2-Oxy-5-chlormethyl-benzaldehyd und den 2-Methoxy-5-chlormethyl-benzaldehyd.
  作者：Benno Reichert、Walter Hoss

  DOI：10.1002/ardp.19422800404

  日期：——
• US6355658B1
  申请人：——

  公开号：US6355658B1

  公开（公告）日：2002-03-12