2-(1-trityl-1H-imidazol-4-yl)benzonitrile | 450415-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-(1-trityl-1H-imidazol-4-yl)benzonitrile
• 英文别名: 2-(1-Trityl-1H-imidazol-4-yl)-benzonitrile；2-(1-tritylimidazol-4-yl)benzonitrile
• CAS: 450415-80-2
• 化学式: C₂₉H₂₁N₃
• 分子量: 411.506
• InChiKey: SMLKYPJICULARP-UHFFFAOYSA-N

物化性质

• 沸点：
  610.4±43.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-trityl-1H-imidazol-4-yl)benzonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 2-(1-trityl-1H-imidazol-4-yl)benzylamine
  参考文献：
  名称：

  Discovery and Evaluation of Potent P₁ Aryl Heterocycle-Based Thrombin Inhibitors

  摘要：

  In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P-1 region. Various benzylamines were coupled to a pyridine/pyrazinone P-2-P-3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K-i of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P-1 aryl heterocycles with a variety of P-2-P-3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P-1 will allow for more diversification in the P-2-P-3 region to ultimately address additional pharmacological concerns.

  DOI：

  10.1021/jm030303e
• 作为产物：
  描述：

  4-(2-溴苯)-1H-咪唑 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 2-(1-trityl-1H-imidazol-4-yl)benzonitrile
  参考文献：
  名称：

  Discovery and Evaluation of Potent P₁ Aryl Heterocycle-Based Thrombin Inhibitors

  摘要：

  In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P-1 region. Various benzylamines were coupled to a pyridine/pyrazinone P-2-P-3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K-i of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P-1 aryl heterocycles with a variety of P-2-P-3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P-1 will allow for more diversification in the P-2-P-3 region to ultimately address additional pharmacological concerns.

  DOI：

  10.1021/jm030303e

文献信息

• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE LA THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002064140A1

  公开（公告）日：2002-08-22

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein R2 is R3 is selected from the group consisting of 1) hydrogen, 2) halogen, 3) C 1-4 alkyl, 4) C 3-7 cycloalkyl, 5) CF3, 6) OCF3, 7) C 1-4 alkoxy, and 8) cyano; and R12 is a 5-membered heteroaryl ring having 2, 3, or 4 heteroatoms, provided that at least 1 heteroatom is N, and at most 1 of the heteroatoms is S, said ring being unsubstituted or substituted, at any one ring atom, with CH3.

  本发明的化合物在抑制凝血酶和相关的血栓闭塞方面有用，其结构如下：或其药学上可接受的盐，其中R2和R3选自以下组：1）氢，2）卤素，3）C 1-4 烷基，4）C 3-7 环烷基，5）CF3，6）OCF3，7）C 1-4 醇基，8）氰基；R12是一个具有2、3或4个杂原子的5元杂环芳基环，其中至少1个杂原子是N，至多1个杂原子是S，所述环未取代或在任何一个环原子上用CH3取代。
• Thrombin inhibitors
  申请人：——

  公开号：US20040097730A1

  公开（公告）日：2004-05-20

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein R2 is R3 is selected from the group consisting of 1) hydrogen, 2) halogen, 3) C 1-4 alkyl, 4) C 3-7 cycloalkyl, 5) CF3, 6) OCF3, 7) C 1-4 alkoxy, and 8) cyano; and R12 is a 5-membered heteroaryl ring having 2, 3, or 4 heteroatoms, provided that at least 1 heteroatom is N, and at most 1 of the heteroatoms is S, said ring being unsubstituted or substituted, at any one ring atom, with CH3. 1

  本发明的化合物具有以下结构，或其药学上可接受的盐，在抑制凝血酶和相关血栓闭塞方面有用，其中R2和R3从以下组中选择：1）氢，2）卤素，3）C 1-4 烷基，4）C 3-7 环烷基，5）CF3，6）OCF3，7）C 1-4 烷氧基和8）氰基；而R12是一个5元杂环芳基环，其中含有2、3或4个杂原子，至少1个杂原子是N，且最多1个杂原子是S，所述环在任何一个环原子上未取代或被取代，该取代基为CH3.
• THROMBIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1359913A1

  公开（公告）日：2003-11-12
• US7026324B2
  申请人：——

  公开号：US7026324B2

  公开（公告）日：2006-04-11
• Discovery and Evaluation of Potent P₁ Aryl Heterocycle-Based Thrombin Inhibitors
  作者：Mary Beth Young、James C. Barrow、Kristen L. Glass、George F. Lundell、Christina L. Newton、Janetta M. Pellicore、Kenneth E. Rittle、Harold G. Selnick、Kenneth J. Stauffer、Joseph P. Vacca、Peter D. Williams、Dennis Bohn、Franklin C. Clayton、Jacquelynn J. Cook、Julie A. Krueger、Lawrence C. Kuo、S. Dale Lewis、Bobby J. Lucas、Daniel R. McMasters、Cynthia Miller-Stein、Beth L. Pietrak、Audrey A. Wallace、Rebecca B. White、Bradley Wong、Youwei Yan、Philippe G. Nantermet

  DOI：10.1021/jm030303e

  日期：2004.6.1

  In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P-1 region. Various benzylamines were coupled to a pyridine/pyrazinone P-2-P-3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K-i of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P-1 aryl heterocycles with a variety of P-2-P-3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P-1 will allow for more diversification in the P-2-P-3 region to ultimately address additional pharmacological concerns.