1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid | 439118-54-4

• 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
• 英文别名: N-(tert-butoxycarbonyl)-3-pyridin-2-yl-D-alanyl-L-proline；(2S)-1-[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pyridin-2-ylpropanoyl]pyrrolidine-2-carboxylic acid
• CAS: 439118-54-4
• 化学式: C₁₈H₂₅N₃O₅
• 分子量: 363.414
• InChiKey: HJNPYQFSLONPJZ-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  109
• 氢给体数：
  2
• 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 在 盐酸 、 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 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-(2(R)-amino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid 5-chloro-2-[1,2,4]triazol-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：

  2-吡啶基丙氨酸 在 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 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 1-(2(R)-tert-butoxycarbonylamino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid
  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 。
• [EN] BENZYLAMINE DERIVATIVES AND THEIR USE AS THROMBIN INHIBITORS<br/>[FR] DERIVES DE BENZYLAMINE ET LEUR UTILISATION COMME INHIBITEURS DE THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002050056A1

  公开（公告）日：2002-06-27

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. where R3 is -CH2NH2, -CH2CH2NH2, or -CH2NHC(O)OC(CH3)3.

  本发明的化合物具有以下结构，或其药学上可接受的盐，例如其中R3为-CH2NH2，-CH2CH2NH2或-CH2NHC（O）OC（CH3）3，对于抑制凝血酶和相关的血栓闭塞非常有用。
• US6515011B2
  申请人：——

  公开号：US6515011B2

  公开（公告）日：2003-02-04
• US7144899B2
  申请人：——

  公开号：US7144899B2

  公开（公告）日：2006-12-05
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002064559A2

  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 Formula (I): wherein u is CH or N; Q is 1)-N(R?25)CH(R30¿)- wherein the nitrogen atom is attached to R?1, and R25 and R30¿ are independently selected from the group consisting of hydrogen, C¿3-6?cycloalkyl, and C1-6alkyl, or 2) wherein the nitrogen atom is attached to R?1¿, and m is 0, 1, or 2.