2-[2-(3-Aminophenyl)-3-chloro-5-(cyclobutylamino)-6-oxopyrazin-1-yl]acetic acid | 308846-24-4

• 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: 2-[2-(3-Aminophenyl)-3-chloro-5-(cyclobutylamino)-6-oxopyrazin-1-yl]acetic acid
• CAS: 308846-24-4
• 化学式: C₁₆H₁₇ClN₄O₃
• 分子量: 348.789
• InChiKey: YENGKGHDFPUPEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[2-(3-Aminophenyl)-3-chloro-5-(cyclobutylamino)-6-oxopyrazin-1-yl]acetic acid 在 palladium on activated charcoal 盐酸 、 PS-DCC 、 氢气 、 1-羟基苯并三唑 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[6-(3-aminophenyl)-5-chloro-3-(cyclobutylamino)-2-oxo-1,2-dihydropyrazin-1-yl]-N-[(4-carbamimidoyl-2,3,5,6-tetrafluorophenyl)methyl]acetamide
  参考文献：
  名称：

  含新型P1针作为TF / VIIa抑制剂的吡嗪酮的设计，合成和生物学评估。

  摘要：

  本文描述了一系列取代的吡嗪酮作为TF / VIIa复合物抑制剂的设计，合成和酶促活性。设计这些抑制剂以探索先前描述的P1 idine的置换和变异[J. 中 Chem.2003，46，4050]。根据与母体苯基am（pKa约为12）相比降低的碱性，选择P1针头替代品。影响化合物口服生物利用度的一个因素是该化合物在肠道中的电离状态。该研究的理想结果是确定一种口服生物利用的TF-VIIa抑制剂。

  DOI：

  10.1016/j.bmcl.2007.05.090
• 作为产物：
  描述：

  [5-Chloro-3-cyclobutylamino-6-(3-nitro-phenyl)-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 2-[2-(3-Aminophenyl)-3-chloro-5-(cyclobutylamino)-6-oxopyrazin-1-yl]acetic acid
  参考文献：
  名称：

  Structure-based drug design of pyrazinone antithrombotics as selective inhibitors of the tissue factor VIIa complex

  摘要：

  Structure-based drug design coupled with polymer-assisted solution-phase library synthesis was utilized to develop a series of pyrazinone inhibitors of the tissue factor/Factor Vila complex. The crystal structure of a tri-peptide ketothiazole complexed with TF/VIIa was utilized in a docking experiment that identified a benzyl-substituted pyrazinone as a P-2 surrogate for the tri-peptide. A 5-step PASP library synthesis of these aryl-substituted pyrazinones was developed. The sequence allows for attachment of a variety of P-1 and P-3 moieties, which led to synthesis pyrazinone 23. Compound 23 exhibited 16 nM IC50 against TF/VIIa with > 6250x selectivity versus 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 primate model of thrombosis. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00410-4

文献信息

• [EN] SUBSTITUTED POLYCYCLIC ARYL AND HETEROARYL PYRAZINONES USEFUL FOR SELECTIVE INHIBITION OF THE COAGULATION CASCADE<br/>[FR] ARYLE POLYCYCLIQUE SUBSTITUTE ET PYRAZINONES D'HETEROARYLE UTILISES DANS L'INHIBITION SELECTIVE DE LA COAGULATION
  申请人：PHARMACIA CORP

  公开号：WO2001087854A1

  公开（公告）日：2001-11-22

  The invention relates to substituted polycyclic aryl and heteroaryl pyrazinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

  本发明涉及替代的多环芳基和杂环芳基吡嗪酮类化合物，用作凝血级联反应中丝氨酸蛋白酶的抑制剂，以及用于治疗和预防各种血栓性疾病，包括冠状动脉和脑血管疾病的抗凝治疗的化合物、组合物和方法。
• Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
  申请人：Pharmacia Corporation

  公开号：US20040102448A1

  公开（公告）日：2004-05-27

  The invention relates to substituted polycyclic aryl and heteroaryl pyrazinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of dirombotic conditions including coronary artery and cerebrovascular diseases.

  本发明涉及用作凝血级联中丝氨酸蛋白酶抑制剂的取代多环芳基和杂环芳基吡嗪酮化合物，以及用于治疗和预防包括冠状动脉和脑血管疾病在内的各种血栓病症的化合物、组合物和抗凝治疗方法。
• SUBSTITUTED POLYCYCLIC ARYL AND HETEROARYL PYRAZINONES USEFUL FOR SELECTIVE INHIBITION OF THE COAGULATION CASCADE
  申请人：Pharmacia Corporation

  公开号：EP1202975A1

  公开（公告）日：2002-05-08
• US6664255B1
  申请人：——

  公开号：US6664255B1

  公开（公告）日：2003-12-16
• US6908919B2
  申请人：——

  公开号：US6908919B2

  公开（公告）日：2005-06-21