[1-Amino-1-[4-(2-amino-ethyl)-phenyl]-meth-(Z)-ylidene]-carbamic acid benzyl ester | 439860-53-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [1-Amino-1-[4-(2-amino-ethyl)-phenyl]-meth-(Z)-ylidene]-carbamic acid benzyl ester
• 英文别名: benzyl N-[amino-[4-(2-aminoethyl)phenyl]methylidene]carbamate
• CAS: 439860-53-4
• 化学式: C₁₇H₁₉N₃O₂
• 分子量: 297.357
• InChiKey: CMHQJLBNMUVNEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1-Amino-1-[4-(2-amino-ethyl)-phenyl]-meth-(Z)-ylidene]-carbamic acid benzyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.33h， 生成
  参考文献：
  名称：

  Synthesis of Potential Thrombin Inhibitors. Incorporation of Tartaric Acid Templates as P2 Proline Mimetics

  摘要：

  With the objective to prepare novel non-peptidic thrombin inhibitors, bioisosteres of the inhibitory tripeptide D-Phe-Pro-Arg chain have been examined. Thus, the P1 Arg was replaced with p-amidinobenzylamine, an elongated homologue of the same and with 2,5-dichloro benzylamine. The P2-P3, D-Phe-Pro, was replaced with a novel tartaric acid template coupled to a series of readily available, mainly lipophilic, amines. Some,of these compounds exhibit promising thrombin inhibition activity in vitro, IC50 similar to5.9 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00426-6
• 作为产物：
  描述：

  Methanesulfonic acid 2-(4-{amino-[(Z)-benzyloxycarbonylimino]-methyl}-phenyl)-ethyl ester 在 sodium azide 、 三苯基膦 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 [1-Amino-1-[4-(2-amino-ethyl)-phenyl]-meth-(Z)-ylidene]-carbamic acid benzyl ester
  参考文献：
  名称：

  Synthesis of Potential Thrombin Inhibitors. Incorporation of Tartaric Acid Templates as P2 Proline Mimetics

  摘要：

  With the objective to prepare novel non-peptidic thrombin inhibitors, bioisosteres of the inhibitory tripeptide D-Phe-Pro-Arg chain have been examined. Thus, the P1 Arg was replaced with p-amidinobenzylamine, an elongated homologue of the same and with 2,5-dichloro benzylamine. The P2-P3, D-Phe-Pro, was replaced with a novel tartaric acid template coupled to a series of readily available, mainly lipophilic, amines. Some,of these compounds exhibit promising thrombin inhibition activity in vitro, IC50 similar to5.9 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00426-6

文献信息

• Design, Parallel Synthesis, and Crystal Structures of Pyrazinone Antithrombotics as Selective Inhibitors of the Tissue Factor VIIa Complex
  作者：John J. Parlow、Brenda L. Case、Thomas A. Dice、Ricky L. Fenton、Michael J. Hayes、Darin E. Jones、William L. Neumann、Rhonda S. Wood、Rhonda M. Lachance、Thomas J. Girard、Nancy S. Nicholson、Michael Clare、Roderick A. Stegeman、Anna M. Stevens、William C. Stallings、Ravi G. Kurumbail、Michael S. South

  DOI：10.1021/jm030131l

  日期：2003.9.1

  Structure-based drug design (SBDD) and polymer-assisted solution-phase (PASP) library synthesis were used to develop a series of pyrazinone inhibitors of the Tissue Factor/Factor Vlla (TF/VIIa) complex. The crystal structure of a tripeptide-alpha-ketothiazole complexed with TF/VIIa was utilized in a docking experiment to identify the pyrazinone core as a starting scaffold. The pyrazinone core could orient the substituents in the correct spatial arrangement to probe the S-1, S-2, and S-3 pockets of the enzyme. A multistep PASP library synthesis was designed to prepare the substituted pyrazinones varying the P-1, P-2, and P-3 moieties. Hundreds of pyrazinone TF/VIIa inhibitors were prepared and tested in several serine protease enzyme assays involved in the coagulation cascade. The inhibitors exhibited modest activity on TF/ VIIa with excellent selectivity over thrombin (Ha) and Factor Xa. The structure-activity relationship of the pyrazinone inhibitors will be discussed and X-ray crystal structures of selected compounds complexed with the TF/VIIa enzyme will be described. This study ultimately led to the synthesis of compound 34, which exhibited 16 nM (IC50) activity on TF/VIIa with >6250x selectivity vs Factor Xa and thrombin. This potent and highly selective inhibitor of TF/VIIa was chosen for preclinical, intravenous proof-of-concept studies to demonstrate the separation between antithrombotic efficacy and bleeding side effects in a nonhuman primate model of electrolytic-induced arterial thrombosis.
• Synthesis of Potential Thrombin Inhibitors. Incorporation of Tartaric Acid Templates as P2 Proline Mimetics
  作者：Anders Dahlgren、Jonas Brånalt、Ingemar Kvarnström、Ingemar Nilsson、Djordje Musil、Bertil Samuelsson

  DOI：10.1016/s0968-0896(01)00426-6

  日期：2002.5

  With the objective to prepare novel non-peptidic thrombin inhibitors, bioisosteres of the inhibitory tripeptide D-Phe-Pro-Arg chain have been examined. Thus, the P1 Arg was replaced with p-amidinobenzylamine, an elongated homologue of the same and with 2,5-dichloro benzylamine. The P2-P3, D-Phe-Pro, was replaced with a novel tartaric acid template coupled to a series of readily available, mainly lipophilic, amines. Some,of these compounds exhibit promising thrombin inhibition activity in vitro, IC50 similar to5.9 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.