3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-3-phenylpropanoic acid | 4958-06-9

• 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: 3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-3-phenylpropanoic acid
• 英文别名: 3-<α-Carboxymethyl-benzyl>-4-hydroxy-cumarin；3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-3-phenyl-propionic acid；warfarin；3-(4-hydroxy-2-oxochromen-3-yl)-3-phenylpropanoic acid
• CAS: 4958-06-9
• 化学式: C₁₈H₁₄O₅
• 分子量: 310.306
• InChiKey: DOMPBMYFWLPPAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile 在 盐酸 作用下， 反应 5.0h， 以95%的产率得到3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-3-phenylpropanoic acid
  参考文献：
  名称：

  4-羟基香豆素-β-芳基丙酸衍生物作为强效抗炎药的新型华法林类似物的合理设计、合成及SAR研究

  摘要：

  高效和增强安全性的抗炎药物的合成已成为药物发现过程中的一项具有挑战性的任务。已经合成了华法林类似物 3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-3-arylpropanoic acid 衍生物库，并通过利用不同的分析技术建立了它们的结构。体外 COX-1/COX-2 研究揭示了选择性化合物2b (IC 50 =180.45 µl/ml)、2c (IC 50 =21.03 µl/ml) 和2f (IC 50 =120.45 µl/ml)的有效效力与参考药物阿司匹林相比，针对 COX-2 (IC 50 =121.60 µl/ml)。化合物2c对 COX-2 的选择性更高，选择性指数为 7.42，而标准阿司匹林的选择性指数为 4.14。此外，还评估了靶分子对 MMP2 和 MMP9 的抗炎活性，结果显示出高百分比的抑制。同时，蛋白质变性研究显示化合物2a (IC 50

  DOI：

  10.1016/j.molstruc.2021.132300

文献信息

• Materials and methods for treating coagulation disorders
  申请人：——

  公开号：US20040220258A1

  公开（公告）日：2004-11-04

  This invention is drawn to compounds which are more easily metabolized by the metabolic drug detoxification systems. Particularly, warfarin analogs which have been designed to include esters within the structure of the compounds are taught. The invention teaches methods of reducing the toxicity of drugs comprising the introduction of ester groups into drugs during the synthesis of the drug. This invention is also drawn to methods of treating coagulation disorders comprising the administration of compounds which have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester containing warfarin, analogs are also taught.

  这项发明涉及一种更容易被代谢药物解毒系统代谢的化合物。特别是，设计了包含酯基的华法林类似物的结构。该发明教导了在药物合成过程中引入酯基以减少药物毒性的方法。这项发明还涉及治疗凝血障碍的方法，包括给予设计为通过血清或细胞内酯酶代谢的化合物。还教导了含有酯基华法林类似物的药物组合物。
• Materials and Methods for Treating Coagulation Disorders
  申请人：Druzgala Pascal

  公开号：US20080221204A1

  公开（公告）日：2008-09-11

  This invention is drawn to compounds which are more easily metabolized by the metabolic drug detoxification systems. Particularly, warfarin analogs which have been designed to include esters within the structure of the compounds are taught. The invention teaches methods of reducing the toxicity of drugs comprising the introduction of ester groups into drugs during the synthesis of the drug. This invention is also drawn to methods of treating coagulation disorders comprising the administration of compounds which have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester containing warfarin, analogs are also taught.

  本发明涉及化合物，这些化合物更容易被代谢药物解毒系统代谢。特别地，本发明涉及华法林类似物，其已被设计为在化合物的结构中包含酯基。本发明教导了在药物合成过程中引入酯基来减少药物毒性的方法。本发明还涉及治疗凝血障碍的方法，包括给予被设计为被血清或细胞内酯酶代谢的化合物。本发明还教导了含有酯基华法林类似物的药物组成物。
• Materials And Methods For Treating Coagulation Disorders
  申请人：Druzgala Pascal

  公开号：US20070129429A1

  公开（公告）日：2007-06-07

  This invention is drawn to compounds which are more easily metabolized by the metabolic drug detoxification systems. Particularly, warfarin analogs which have been designed to include esters within the structure of the compounds are taught. The invention teaches methods of reducing the toxicity of drugs comprising the introduction of ester groups into drugs during the synthesis of the drug. This invention is also drawn to methods of treating coagulation disorders comprising the administration of compounds which have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester containing warfarin, analogs are also taught.

  本发明涉及一种化合物，该化合物更易于被代谢药物解毒系统代谢。特别是，本发明教授了设计在化合物结构中包含酯基的华法林类似物。本发明教授了一种通过在药物合成过程中引入酯基来减少药物毒性的方法。本发明还涉及一种治疗凝血障碍的方法，该方法包括给予已经设计成可以被血清或细胞内水解酶和酯酶代谢的化合物。本发明还涉及含有酯基华法林类似物的制药组合物。
• Materials and Methods For Treating Coagulation Disorders
  申请人：Druzgala Pascal

  公开号：US20080027132A1

  公开（公告）日：2008-01-31

  The subject invention provides anticoagulant compounds of formula I: and pharmaceutically acceptable salts thereof, wherein R 1 , R 3 , n and Ar are as defined herein. The compounds of the subject invention can be used to treat at-risk populations thereby bringing relief of symptoms, improving the quality of life, preventing acute and long-term complications, reducing mortality and treating accompanying disorders. The invention further comprises pharmaceutical compositions comprising the compounds and salts of the invention, as well as methods of using the compounds, salts, and compositions of the invention.

  本发明提供了公式I的抗凝剂化合物及其药学上可接受的盐，其中R1、R3、n和Ar的定义如本文所述。本发明的化合物可用于治疗处于风险中的人群，从而缓解症状、改善生活质量、预防急性和长期并发症、降低死亡率和治疗伴随疾病。本发明还包括包含该化合物和该发明的盐的制药组合物，以及使用该化合物、盐和组合物的方法。
• Materials and methods for treating coagulation disorders
  申请人：ARYx Therapeutics

  公开号：EP2161261A1

  公开（公告）日：2010-03-10

  A compound according to Formula VI, or a pharmaceutically acceptable salt thereof, for the treatment of coagulation disorders, wherein, R is C1-C8 alkyl substituted with at least one halogen; R is C2-C8 alkyl substituted with at least one halogen; R is C3-C7 alkyl substituted with at least one halogen; R is C3-C6 alkyl substituted with at least one halogen.

  用于治疗凝血障碍的符合式 VI 的化合物或其药学上可接受的盐、 其中 R 是被至少一种卤素取代的 C1-C8 烷基； R 是被至少一种卤素取代的 C2-C8 烷基 R 是被至少一种卤素取代的 C3-C7 烷基 R 是被至少一种卤素取代的 C3-C6 烷基。