ATI-5900 | 867257-31-6

• 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: ATI-5900
• 英文别名: 4-(4-Hydroxy-2-oxo-2H-chromen-3-ylmethyl)-benzoic acid；4-[(4-Hydroxy-2-oxochromen-3-yl)methyl]benzoic acid
• CAS: 867257-31-6
• 化学式: C₁₇H₁₂O₅
• 分子量: 296.279
• InChiKey: UDWNNSWBUADNBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ATI-5900 、 1,1,1,3,3,3-六氟-2-甲基-2-丙醇 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 以71%的产率得到1,1,1,3,3,3-六氟-2-甲基丙烷-2-基4-[(4-羟基-2-氧代-2H-苯并吡喃-3-yl)甲基]苯甲酸酯
  参考文献：
  名称：

  一种替卡法林的制备方法

  摘要：

  本发明涉及一种替卡法林的制备方法，以对醛基苯甲酸和4‑羟基香豆素为底物，进行加成反应，再与1,1,1,3,3,3‑六氟叔丁醇缩合得到终产物替卡法林，该方法避免了现有技术中高温条件下进行缩合反应引起的酯水解杂质，纯度及收率大幅提升，且操作简单，后处理方便，更适于工业化生产。

  公开号：

  CN107176940B
• 作为产物：
  描述：

  1,1,1,3,3,3-六氟-2-甲基丙烷-2-基4-[(4-羟基-2-氧代-2H-苯并吡喃-3-yl)甲基]苯甲酸酯 在 carboxylesterase 作用下， 生成 ATI-5900
  参考文献：
  名称：

  Identification of VKORC1 genotype leading to resistance to tecarfarin

  摘要：

  The VKORC1 gene codes for the VKORC1 enzyme that is responsible for the reduction of vitamin K epoxide into vitamin K. VKORC1 enzyme is the target of vitamin K antagonists (VKA). The use of VKA in human medicine is difficult because of inter-individual variability in VKA requirements. This variability is partly due to basic physiological parameters but also to genetic polymorphisms in CYP2C9 involved in VKA metabolism. Tecarfarin, a new VKA, was developed to avoid the CYP2C9-dependent metabolism. This molecule is metabolized by carboxylesterases. Nevertheless, genetic variations in the VKORC1 gene are also associated with inter-individual variability in VKA requirements. This study was performed to estimate the benefit of using tecarfarin versus traditional VKA in human patient carrier for hVKORC1 mutation. Wild type hVKORC1 and its spontaneous mutants were expressed in Pichia pastoris and susceptibility to tecarfarin was assessed by the in vitro determination of inhibition constants. Among the 14 mutated VKORC1 proteins analyzed in this study, 6 mutations (i.e., A26P, A41S, V54L, H68Y, I123N, and Y139H) led to resistant to traditional VKAs, while only 4 mutations (i. e., A26P, V54L, I123N, and Y139H) led to resistant to tecarfarin. Compared to other VKAs, a clear benefit of tecarfarin is observed for the mutants A26P, A41S, H68Y, and I123N and an absence of benefit for the mutant Y139H. Finally, tecarfarin is particularly inefficient on V54L-VKORC1.

  DOI：

  10.1002/jcph.332

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。
• [EN] MATERIALS AND METHODS FOR TREATING COAGULATION DISORDERS<br/>[FR] MATERIAUX ET PROCEDES DE TRAITEMENT DE TROUBLES DE LA COAGULATION
  申请人：ARYX THERAPEUTICS

  公开号：WO2005100336A1

  公开（公告）日：2005-10-27

  The subject invention provides anticoagulant compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R3, 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高风险人群，从而缓解症状，提高生活质量，预防急性和长期并发症，降低死亡率并治疗伴随的疾病。本发明还包括包含该化合物和该发明中盐的制药组合物，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：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。