benzyl 2-trifluoromethylsulfonyloxy-5-formylbenzoate | 239462-58-9

• 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: benzyl 2-trifluoromethylsulfonyloxy-5-formylbenzoate
• 英文别名: Benzyl 5-formyl-2-(trifluoromethylsulfonyloxy)benzoate
• CAS: 239462-58-9
• 化学式: C₁₆H₁₁F₃O₆S
• 分子量: 388.321
• InChiKey: OPLUNGZJCVSHAH-UHFFFAOYSA-N

物化性质

• 沸点：
  503.5±50.0 °C(Predicted)
• 密度：
  1.487±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzyl 2-trifluoromethylsulfonyloxy-5-formylbenzoate 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium chlorite 、 N-羟基-7-氮杂苯并三氮唑 、 sodium dihydrogenphosphate dihydrate 、 2-甲基-2-丁烯 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸酐 、 copper(II) oxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 叔丁醇 为溶剂， 生成 tert-butyl 2-[2-[[1-[(2,4-dimethoxyphenyl)methylamino]isoquinolin-6-yl]carbamoyl]-6-oxo-1H-pyridin-3-yl]-5-(2,2-dimethylpropylcarbamoyl)benzoate
  参考文献：
  名称：

  Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold

  摘要：

  In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIla inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIla is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor Vlla. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.06.028
• 作为产物：
  描述：

  5-甲酰水杨酸 在 吡啶 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl 2-trifluoromethylsulfonyloxy-5-formylbenzoate
  参考文献：
  名称：

  Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold

  摘要：

  In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIla inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIla is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor Vlla. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.06.028

文献信息

• [EN] TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS SERINE PROTEASE INHIBITORS<br/>[FR] DERIVES DE TETRAHYDROQUINOLINE UTILES EN TANT QU'INHIBITEURS DE SERINE PROTEASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004080971A1

  公开（公告）日：2004-09-23

  The present invention provides compounds of Formula (I) ; or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4, R4, R5, R13, R14, R15 and R16 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了式（I）的化合物；或其立体异构体或药用可接受的盐形式，其中变量A、B、L1、L2、X1、X2、X3、X4、R4、R5、R13、R14、R15和R16如本文所定义。式（I）的化合物可用作凝血级联和/或接触激活系统的丝氨酸蛋白酶酶的选择性抑制剂；例如凝血酶、因子Xa、因子XIa、因子IXa、因子VIIa和/或血浆激肽。具体而言，涉及选择性因子XIa抑制剂的化合物。本发明还涉及包含这些化合物的药物组合物以及使用它们治疗血栓栓塞和/或炎症性疾病的方法。
• Biarylmethyl indolines, indoles and tetrahydroquinolines, useful as serine protease inhibitors
  申请人：——

  公开号：US20040220206A1

  公开（公告）日：2004-11-04

  The present invention provides compounds of Formula (I): 1 or a stereoisomer or pharmaceutically acceptable salt or hydrate form thereof, wherein the variables A, B, L 1 , L 2 , X 1 , X 2 , X 3 , X 4 and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了Formula (I)的化合物：1或其立体异构体或药用可接受的盐或水合物形式，其中变量A、B、L1、L2、X1、X2、X3、X4和W如本文所定义。Formula (I)的化合物可作为凝血级联和/或接触激活系统的丝氨酸蛋白酶酶的选择性抑制剂，例如凝血酶、因子Xa、因子XIa、因子IXa、因子VIIa和/或血浆激肽。具体地，涉及具有选择性因子XIa抑制剂的化合物。本发明还涉及包含这些化合物的药物组合物以及使用这些药物组合物治疗血栓栓塞性和/或炎症性疾病的方法。
• Tetrahydroquinoline derivatives as antithrombotic agents
  申请人：——

  公开号：US20030225110A1

  公开（公告）日：2003-12-04

  This invention relates generally to tetracyclic tetrahydroquinoline compounds, and analogues thereof, and pharmaceutically acceptable salt forms thereof, which are selective inhibitors of serine protease enzymes, especially factor VIIa; pharmaceutical compositions containing the same; and methods of using the same as anticoagulant agents for modulation of the coagulation cascade.

  这项发明通常涉及四环四氢喹啉化合物及其类似物，以及其药用盐形式，这些化合物是选择性抑制丝氨酸蛋白酶酶，特别是VIIa因子的；含有同样化合物的药物组合物；以及将其用作抗凝剂调节凝血级联的方法。
• Amidino derivatives and drugs containing the same as the active ingredient
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06358960B1

  公开（公告）日：2002-03-19

  The novel amidino derivatives of the formula (I): wherein all the symbols are as in specification defined; have an inhibitory activity of a blood coagulation factor VIIa and are useful for treatment and/or prevention of several angiopathy caused by enhancing a coagulation activity, such as disseminated intravascular coagulation, coronary thrombosis, cerebral infarction, cerebral embolism, transient ischemic attack, cerebrovascular disorders, pulmonary vascular diseases, deep venous thrombosis, peripheral arterial obstruction, thrombosis after artificial vascular transplantation and artificial valve transplantation, post-operative thrombosis, reobstruction and restenosis after coronary artery bypass operation, reobstruction and restenosis after PTCA or PTCR, thrombosis by extracorporeal circulation and procoagulative diseases such as glomerlonephriitis.

  该式(I)的胍基衍生物小说：其中所有符号均如规范中所定义；具有抑制血凝血因子VIIa的活性，并可用于治疗和/或预防由增强凝血活性引起的多种血管病，如弥散性血管内凝血、冠状动脉血栓形成、脑梗死、脑栓塞、短暂性缺血发作、脑血管疾病、肺血管疾病、深静脉血栓形成、周围动脉阻塞、人工血管移植后血栓形成和人工瓣膜移植后血栓形成、术后血栓形成、冠状动脉旁路手术后再阻塞和再狭窄、PTCA或PTCR后再阻塞和再狭窄、体外循环引起的血栓形成以及像肾小球肾炎这样的促凝病。
• AMIDINO DERIVATIVES AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1078917A1

  公开（公告）日：2001-02-28

  The novel amidino derivatives of the formula (I): wherein all the symbols are as in specification defined; have an inhibitory activity of a blood coagulation factor VIIa and are useful for treatment and / or prevention of several angiopathy caused by enhancing a coagulation activity, such as disseminated intravascular coagulation, coronary thrombosis, cerebral infarction, cerebral embolism, transient ischemic attack, cerebrovascular disorders, pulmonary vascular diseases, deep venous thrombosis, peripheral arterial obstruction, thrombosis after artificial vascular transplantation and artificial valve transplantation, post-operative thrombosis, reobstruction and restenosis after coronary artery bypass operation, reobstruction and restenosis after PTCA or PTCR, thrombosis by extracorporeal circulation and procoagulative diseases such as glomerlonephriitis.

  式 (I) 的新型脒基衍生物： 其中所有符号与说明书中的定义相同； 具有抑制凝血因子 VIIa 的活性，可用于治疗和/或预防因增强凝血活性而引起的多种血管病变，如弥散性血管内凝血、冠状动脉血栓形成、脑梗塞、脑栓塞、短暂性脑缺血发作、脑血管疾病、肺血管疾病、深静脉血栓形成、外周动脉阻塞、人工血管移植后的血栓形成、深静脉血栓形成、外周动脉阻塞、人工血管移植和人工瓣膜移植术后血栓形成、术后血栓形成、冠状动脉搭桥术后再梗阻和再狭窄、PTCA 或 PTCR 术后再梗阻和再狭窄、体外循环血栓形成以及肾小球肾炎等促凝血疾病。