ethyl 4-(ω-bromoacetyl)phenylacetate | 55453-49-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-(ω-bromoacetyl)phenylacetate
• 英文别名: Ethyl [4-(bromoacetyl)phenyl]acetate；ethyl 2-[4-(2-bromoacetyl)phenyl]acetate
• CAS: 55453-49-1
• 化学式: C₁₂H₁₃BrO₃
• 分子量: 285.137
• InChiKey: LSLGMUQLSVUSOI-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：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(ω-bromoacetyl)phenylacetate 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成
  参考文献：
  名称：

  [EN] FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
  [FR] HETEROCYCLES A CINQ CHAINONS UTILISES COMME INHIBITEURS DE LA SERINE PROTEASE

  摘要：

  公开号：

  WO2005123050A3
• 作为产物：
  描述：

  4-乙酰基苯乙酸乙酯 在 溴 、 sodium acetate 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 ethyl 4-(ω-bromoacetyl)phenylacetate
  参考文献：
  名称：

  Antimicrobial (2-nitro-3-benzofuranyl)phenylacetic acids

  摘要：

  描述了作为抗微生物剂活性的(2-硝基-3-苯并呋喃基)苯乙酸，以及它们的制备方法和中间体。

  公开号：

  US04066782A1

文献信息

• Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles
  作者：Larry J. Powers、S. W. Fogt、Z. S. Ariyan、D. J. Rippin、R. D. Heilman、Richard J. Matthews

  DOI：10.1021/jm00137a022

  日期：1981.5

  The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes, such as the incorporation of a gem-dimethyl substituent in the 6 position, increase

  描述了结构变化对一系列咪唑并噻唑和噻唑基苯并咪唑的生物活性的影响。发现在环系统的2或3位具有极性取代基的化合物在维持抗炎活性的同时毒性较小。其他结构变化，例如在6位掺入宝石二甲基取代基，会增加急性毒性并消除抗炎活性。具有最佳活性/毒性比的化合物在噻唑环上包含烷基磺酰基取代基。噻唑并苯并咪唑类似物比咪唑类似物更有效。
• Synthesis and in vitro kinetic evaluation of N-thiazolylacetamido monoquaternary pyridinium oximes as reactivators of sarin, O-ethylsarin and VX inhibited human acetylcholinesterase (hAChE)
  作者：Aditya Kapil Valiveti、Uma M. Bhalerao、Jyotiranjan Acharya、Hitendra N. Karade、Badri Narayan Acharya、G. Raviraju、Anand K. Halve、Mahabir Parshad Kaushik

  DOI：10.1016/j.bmc.2015.05.027

  日期：2015.8

  the newly synthesized oximes were evaluated for their physicochemical parameters (pKa) and correlated with their respective reactivation efficacies to assess the capability of the oxime reactivator. Three of these novel compounds showed promising reactivation efficacies toward OP inhibited hAChE. Molecular docking studies were performed in order to correlate the reactivation efficacies with their interactions

  由于各种药理和毒理学原因，目前可用的用于治疗有机磷中毒的药物不够有效。在这方面，我们在此报告了一系列N-噻唑基乙酰胺单季吡啶鎓肟及其类似物（1a - 1b至6a - 6b）的合成，并带有不同取代的噻唑环，并评估了它们在体外对神经毒剂（沙林，O-乙基沙林和VX）抑制人红细胞乙酰胆碱酯酶（h AChE）。进行再活化动力学以确定解离常数（K D），反应速率常数（K D）。k r）和所有化合物的二阶速率常数（k r2），并将其功效与市售解毒剂进行比较。2-PAM和obidoxime。评价所有新合成的肟的理化参数（p K a），并将其与各自的再活化效率相关联，以评估肟再活化剂的能力。这些新颖的化合物中的三个显示出对OP抑制h AChE有希望的再激活作用。进行了分子对接研究，以使再活化效率与其在AChE活性位点的相互作用相关联。
• Five-membered heterocycles useful as serine protease inhibitors
  申请人：Hangeland J. Jon

  公开号：US20050282805A1

  公开（公告）日：2005-12-22

  The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R 3 , R 4 , R 6 , R 11 , X 1 , X 2 , and X 3 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 provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

  本发明提供了一种治疗血栓性或炎症性疾病的方法，即向需要治疗的患者施用至少一种公式（I）或公式（V）化合物的治疗有效量，或其立体异构体或药学上可接受的盐或溶剂形式，其中变量A、L、Z、R3、R4、R6、R11、X1、X2和X3如本文所定义。公式（I）化合物可用作凝血级联和/或接触激活系统中丝氨酸蛋白酶酶的选择性抑制剂；例如凝血酶、Xa因子、XIa因子、IXa因子、VIIa因子和/或血浆激肽。特别是，涉及到选择性因子XIa抑制剂的化合物。本发明还提供了公式I范围内的化合物，并涉及包含这些化合物的制药组合物。
• FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
  申请人：Hangeland Jon J.

  公开号：US20090036438A1

  公开（公告）日：2009-02-05

  The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R 3 , R 4 , R 6 , R 11 , X 1 , X 2 , and X 3 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 provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

  本发明提供了一种治疗血栓性或炎症性疾病的方法，该方法向需要治疗的患者施用至少一种公式（I）或公式（V）中的化合物的治疗有效量：或其立体异构体或药学上可接受的盐或溶剂形式，其中变量A、L、Z、R3、R4、R6、R11、X1、X2和X3如本文所定义。公式（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。特别是，涉及到选择性因子XIa抑制剂的化合物。本发明还提供了公式I范围内的化合物，并涉及包含这些化合物的制药组合物。
• Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity
  作者：Jon J. Hangeland、Todd J. Friends、Karen A. Rossi、Joanne M. Smallheer、Cailan Wang、Zhong Sun、James R. Corte、Tianan Fang、Pancras C. Wong、Alan R. Rendina、Frank A. Barbera、Jeffrey M. Bozarth、Joseph M. Luettgen、Carol A. Watson、Ge Zhang、Anzhi Wei、Vidhyashankar Ramamurthy、Paul E. Morin、Gregory S. Bisacchi、Srinath Subramaniam、Piramanayagam Arunachalam、Arvind Mathur、Dietmar A. Seiffert、Ruth R. Wexler、Mimi L. Quan

  DOI：10.1021/jm5010607

  日期：2014.12.11

  Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (K-i = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg(-1) h(-1)). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.