benzyl (NE)-N-[amino-[4-[[[(2S)-pyrrolidine-2-carbonyl]amino]methyl]phenyl]methylidene]carbamate | 187752-79-0

• 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: benzyl (NE)-N-[amino-[4-[[[(2S)-pyrrolidine-2-carbonyl]amino]methyl]phenyl]methylidene]carbamate
• CAS: 187752-79-0
• 化学式: C₂₁H₂₄N₄O₃
• 分子量: 380.447
• InChiKey: UVXXAPAMOVHIAR-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (NE)-N-[amino-[4-[[[(2S)-pyrrolidine-2-carbonyl]amino]methyl]phenyl]methylidene]carbamate 在 palladium on activated charcoal 2,6-二甲基吡啶 、 氢气 、 三氟乙酸 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin

  摘要：

  Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P-1, P-2, and P-3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the D-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P-3 subunit in the hydrophobic S-3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.075
• 作为产物：
  描述：

  tert-butyl (S)-2-((4-(N-((benzyloxy)carbonyl)carbamimidoyl)benzyl)carbamoyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到benzyl (NE)-N-[amino-[4-[[[(2S)-pyrrolidine-2-carbonyl]amino]methyl]phenyl]methylidene]carbamate
  参考文献：
  名称：

  Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin

  摘要：

  Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P-1, P-2, and P-3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the D-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P-3 subunit in the hydrophobic S-3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.075

文献信息

• PROLINAMIADE DERIVATIVES AS THROMBIN INHIBITOR, PREPRARATION METHOD AND APPLICATION THEREOF
  申请人：Li Min

  公开号：US20130296245A1

  公开（公告）日：2013-11-07

  Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

  提供了一种化合物的公式(I)，其药用盐，制备方法以及用于抑制凝血酶的应用，以及在治疗和预防凝血酶介导和相关疾病中的应用。
• PROLINAMIDE DERIVATIVE AS THROMBIN INHIBITOR, PREPARATION METHOD AND APPLICATION THEREOF
  申请人：Shanghai Institute of Pharmaceutical Industry

  公开号：EP2639230A1

  公开（公告）日：2013-09-18

  Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

  本发明提供了一种用于抑制凝血酶的式(I)化合物、其药学上可接受的盐、制备方法及其应用，以及在治疗和预防凝血酶介导的疾病和凝血酶相关疾病中的应用。
• Prolinamide derivative as thrombin inhibitor, preparation method and application thereof
  申请人：Shanghai Institute of Pharmaceutical Industry

  公开号：EP2824097A1

  公开（公告）日：2015-01-14

  Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

  本发明提供了一种用于抑制凝血酶的式(I)化合物、其药学上可接受的盐、制备方法及其应用，以及在治疗和预防凝血酶介导的疾病和凝血酶相关疾病中的应用。
• US9434760B2
  申请人：——

  公开号：US9434760B2

  公开（公告）日：2016-09-06
• Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin
  作者：Stephen Hanessian、Karolina Ersmark、Xiaotian Wang、Juan R. Del Valle、Niklas Blomberg、Yafeng Xue、Ola Fjellström

  DOI：10.1016/j.bmcl.2007.03.075

  日期：2007.6

  Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P-1, P-2, and P-3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the D-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P-3 subunit in the hydrophobic S-3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs. (c) 2007 Elsevier Ltd. All rights reserved.