N-(6-bromo-1-isoquinolinyl)benzamide | 215453-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-(6-bromo-1-isoquinolinyl)benzamide
• 英文别名: N-(6-bromoisoquinolin-1-yl)benzamide
• CAS: 215453-27-3
• 化学式: C₁₆H₁₁BrN₂O
• 分子量: 327.18
• InChiKey: KCMIAFQGVQFTEN-UHFFFAOYSA-N

物化性质

• 沸点：
  413.0±25.0 °C(Predicted)
• 密度：
  1.544±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(6-bromo-1-isoquinolinyl)benzamide 在 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 sodium ethanolate 、 溶剂黄146 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 rac-6-(1-aminoisoquinolinyl)alanine
  参考文献：
  名称：

  1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors

  摘要：

  Replacement of the highly basic benzamidine moiety of NAPAP by the moderately basic 1-aminoisoquinoline moiety resulted in thrombin inhibitors with improved selectivity towards trypsin and enhanced Caco-2 cell permeability. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00069-4
• 作为产物：
  描述：

  6-溴异喹啉 在 吡啶 、 乙酸铵 、 盐酸 、 氢氧化钾 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 生成 N-(6-bromo-1-isoquinolinyl)benzamide
  参考文献：
  名称：

  1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors

  摘要：

  Replacement of the highly basic benzamidine moiety of NAPAP by the moderately basic 1-aminoisoquinoline moiety resulted in thrombin inhibitors with improved selectivity towards trypsin and enhanced Caco-2 cell permeability. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00069-4

文献信息

• Heterocyclic derivatives and their use as antithrombotic agents
  申请人：Akzo Nobel N.V.

  公开号：US06194409B1

  公开（公告）日：2001-02-27

  The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is O or S; X′ being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents.

  本发明涉及抗血栓化合物，包括Q基团，其中Q具有化学式(I)，其中亚结构(i)是从(a、b和c)中选定的结构，其中X为O或S；X′独立地为CH或N；m为0、1、2或3；其中基团Q通过氧原子或可选择取代的氮或碳原子结合，或其药学上可接受的盐或前药。本发明的化合物具有治疗活性，特别是抗血栓作用剂。
• Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors
  作者：Peter Ray、Jane Wright、Julia Adam、Johnathan Bennett、Sylviane Boucharens、Darcey Black、Andrew Cook、Angus R. Brown、Ola Epemolu、Dan Fletcher、Anders Haunso、Margaret Huggett、Phil Jones、Steven Laats、Amanda Lyons、Jordi Mestres、Jos de Man、Richard Morphy、Zoran Rankovic、Brad Sherborne、Lorcan Sherry、Nicole van Straten、Paul Westwood、Guido Z.R. Zaman

  DOI：10.1016/j.bmcl.2010.11.060

  日期：2011.1

  Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in the primary ROCK-I IMAP assay. Compounds 23A and 23E were selected as fragment optimized hits for further profiling. Compound 23A has similar ROCK-1 affinity, potency and cell based efficacy to the first generation ROCK inhibitors, however, it has a superior PK profile in C57 mouse. Compound 23E demonstrates the feasibility of improving ROCK-1 affinity, potency and cell based efficacy for the series, however, it has a poor PK profile relative to 23A. (C) 2010 Published by Elsevier Ltd.
• Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa
  作者：Sochanchingwung Rumthao、Oukseub Lee、Qi Sheng、WenTao Fu、Debbie C. Mulhearn、David Crich、Andrew D. Mesecar、Michael E. Johnson

  DOI：10.1016/j.bmcl.2004.07.054

  日期：2004.10

  We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within the oxyanion bole region of the catalytic site substantially enhances activity, with small flexible groups favored over bulkier ones. Ab initio pK(a) calculations suggest that the hydroxyl substituent frequently used for benzamidine moieties may be ionized to form an anionic group, consistent with the general trend. One nonamidine based substituent also shows promising activity. (C) 2004 Elsevier Ltd. All rights reserved.
• US6194409B1
  申请人：——

  公开号：US6194409B1

  公开（公告）日：2001-02-27
• US6432955B1
  申请人：——

  公开号：US6432955B1

  公开（公告）日：2002-08-13