4-Chloro-o-xylendiphthalamid | 52402-00-3

• 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: 4-Chloro-o-xylendiphthalamid
• 英文别名: C,C'-(4-chloro-o-phenylene)-bis-methylamine；1,2-bis-aminomethyl-4-chloro-benzene；4-chloro-1,2-benzenedimethanamine；4-chloro-1,2-di(aminomethyl)benzene；(4-Chlorobenzene-1,2-diyl)dimethanamine；[2-(aminomethyl)-4-chlorophenyl]methanamine
• CAS: 52402-00-3
• 化学式: C₈H₁₁ClN₂
• 分子量: 170.642
• InChiKey: OPYZUJUKJWFWGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Chloro-o-xylendiphthalamid 在 吡啶 、 sodium hydroxide 、 磺酰胺 作用下， 生成 2,4-diallyl-7-chloro-1,2,4,5-tetrahydro-benzo[d][1,2,7]thiadiazepine 3,3-dioxide
  参考文献：
  名称：

  1,2,4,5-Tetrahydro-3,2,4-benzothiadiazepin-3,3-dioxide und 1,2,3,5,6,7-Hexahydro-4,3,5-benzothiadiazonin-4,4-dioxide

  摘要：

  DOI：

  10.1007/bf00911294
• 作为产物：
  描述：

  N,N'-(4-chloro-o-phenylenedimethyl)-bis-phthalimide 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 4-Chloro-o-xylendiphthalamid
  参考文献：
  名称：

  1,2,4,5-Tetrahydro-3,2,4-benzothiadiazepin-3,3-dioxide und 1,2,3,5,6,7-Hexahydro-4,3,5-benzothiadiazonin-4,4-dioxide

  摘要：

  DOI：

  10.1007/bf00911294

文献信息

• 2-(Aminomethyl)-5-Chlorobenzylamide Derivatives and their use as Inhibitors of the Clotting Factor Xa
  申请人：Steinmetzer Torsten

  公开号：US20090117185A1

  公开（公告）日：2009-05-07

  The invention relates to 2-(aminomethyl)-5-chlorobenzylamide derivatives and their use as inhibitors of coagulation factor Xa. The compounds are suitable for the treatment and prophylaxis of cardiovascular and thrombotic events.

  该发明涉及2-(氨甲基)-5-氯苄酰胺衍生物及其作为凝血因子Xa抑制剂的用途。这些化合物适用于治疗和预防心血管和血栓事件。
• Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement
  作者：Harry R. Chobanian、Barbara Pio、Yan Guo、Hong Shen、Mark A. Huffman、Maria Madeira、Gino Salituro、Jenna L. Terebetski、James Ormes、Nina Jochnowitz、Lizbeth Hoos、Yuchen Zhou、Dale Lewis、Brian Hawes、Lyndon Mitnaul、Kim O’Neill、Kenneth Ellsworth、Liangsu Wang、Tesfaye Biftu、Joseph L. Duffy

  DOI：10.1021/acsmedchemlett.5b00047

  日期：2015.5.14

  Modification of the previously disclosed (S)-N-(2-aminmethyl-5-chlorobenzyl)-1-((R)-2-hydroxy-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamide 2 by optimization of the P3 group afforded novel, low molecular weight thrombin inhibitors. Heterocycle replacement of the hydroxyl functional group helped maintain thrombin in vitro potency while improving the chemical stability and pharmacokinetic profile. These modifications led to the identification of compound 10, which showed excellent selectivity over related serine proteases as well as in vivo efficacy in the rat arteriovenous shunt. Compound 10 exhibited significantly improved chemical stability and pharmacokinetic properties over 2 and may be utilized as a structurally differentiated preclinical tool comparator to dabigatran etexilate (Pro-1) to interrogate the on- and off-target effects of oral direct thrombin inhibitors.
• TRYPSIN-LIKE SERINE PROTEASE INHIBITORS, THEIR PREPARATION AND USE AS SELECTIVE INHIBITORS OF THE CLOTTING FACTORS IIA AND XA
  申请人：The Medicines Company (Leipzig) GmbH

  公开号：EP2655399B1

  公开（公告）日：2017-09-27
• P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold
  作者：Philippe G. Nantermet、Christopher S. Burgey、Kyle A. Robinson、Janetta M. Pellicore、Christina L. Newton、James Z. Deng、Harold G. Selnick、S. Dale Lewis、Bobby J. Lucas、Julie A. Krueger、Cynthia Miller-Stein、Rebecca B. White、Bradley Wong、Daniel R. McMasters、Audrey A. Wallace、Joseph J. Lynch、Youwei Yan、Zhongguo Chen、Lawrence Kuo、Stephen J. Gardell、Jules A. Shafer、Joseph P. Vacca、Terry A. Lyle

  DOI：10.1016/j.bmcl.2005.03.110

  日期：2005.6

  In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).
• Design, synthesis and SAR of a series of 1,3,5-trisubstituted benzenes as thrombin inhibitors
  作者：Richard C.A. Isaacs、Christina L. Newton、Kellie J. Cutrona、Swati P. Mercer、Linda S. Payne、Kenneth J. Stauffer、Peter D. Williams、Jacquelynn J. Cook、Julie A. Krueger、S. Dale Lewis、Bobby J. Lucas、Elizabeth A. Lyle、Joseph J. Lynch、Daniel R. McMasters、Adel M. Naylor-Olsen、Maria T. Michener、Audrey A. Wallace

  DOI：10.1016/j.bmcl.2010.12.105

  日期：2011.3

  A novel 1,3,5-trisubstituted benzamide thrombin inhibitor template was designed via hybridization of a known aminopyridinoneacetamide and a known 1,3,5-trisubstituted phenyl ether. Optimization of this lead afforded a novel potent series of biaryl 1,3,5-trisubstituted benzenes with excellent functional anticoagulant potency. (C) 2010 Elsevier Ltd. All rights reserved.