1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid methyl ester | 439116-81-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid methyl ester
• 英文别名: N-(tert-butoxycarbonyl)-3-pyridin-2-yl-D-alanyl-L-proline methyl ester；methyl (2S)-1-[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pyridin-2-ylpropanoyl]pyrrolidine-2-carboxylate
• CAS: 439116-81-1
• 化学式: C₁₉H₂₇N₃O₅
• 分子量: 377.44
• InChiKey: DHEAXHXISVNESK-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid methyl ester 在 盐酸 、 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (S)-1-((R)-2-Amino-3-pyridin-2-yl-propionyl)-pyrrolidine-2-carboxylic acid 5-chloro-2-tetrazol-1-yl-benzylamide
  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：

  L-脯氨酸甲酯盐酸盐 、 2-吡啶基丙氨酸 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以64%的产率得到1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid methyl ester
  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

• Thrombin inhibitors
  申请人：——

  公开号：US20020119992A1

  公开（公告）日：2002-08-29

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 or a pharmaceutically acceptable salt thereof, e.g. where R 3 is —CH 2 NH 2 , —CH 2 CH 2 NH 2 , or —CH 2 NHC(O)OC(CH 3 ) 3 .

  该发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构： 1 或其药用可接受的盐，例如其中R 3 为—CH 2 NH 2 ，—CH 2 CH 2 NH 2 ，或—CH 2 NHC(O)OC(CH 3 ) 3 。
• US6515011B2
  申请人：——

  公开号：US6515011B2

  公开（公告）日：2003-02-04
• 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.