(6S)-N-[(4-carbamimidoylphenyl)methyl]-1-chloro-3-[[1-(hydroxymethyl)cyclopentyl]amino]-8,8-dimethyl-4-oxo-6,7-dihydropyrrolo[1,2-a]pyrazine-6-carboxamide | 773847-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: (6S)-N-[(4-carbamimidoylphenyl)methyl]-1-chloro-3-[[1-(hydroxymethyl)cyclopentyl]amino]-8,8-dimethyl-4-oxo-6,7-dihydropyrrolo[1,2-a]pyrazine-6-carboxamide
• CAS: 773847-41-9
• 化学式: C₂₄H₃₁ClN₆O₃
• 分子量: 487.002
• InChiKey: BPRGJAAARBNIQY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  144
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-甲基1-(2-甲基-2-丙基)4,4-二甲基-5-氧代-1,2-吡咯烷二羧酸酯 在 三氟化硼乙醚 、 三乙基硼氢化锂 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 生成 (6S)-N-[(4-carbamimidoylphenyl)methyl]-1-chloro-3-[[1-(hydroxymethyl)cyclopentyl]amino]-8,8-dimethyl-4-oxo-6,7-dihydropyrrolo[1,2-a]pyrazine-6-carboxamide
  参考文献：
  名称：

  Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF–FVIIa inhibitors

  摘要：

  Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF-FVIIa inhibitors. SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups. An Xray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets. Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.094

文献信息

• Amino-bicyclic pyrazinones and pyridinones as coagulation serine protease inhibitors
  申请人：Zhang Xiaojun

  公开号：US20050038030A1

  公开（公告）日：2005-02-17

  The present invention relates generally to compounds that inhibit serine proteases. In particular it is directed to novel amino-bicyclic pyrazinone and pyridinone compounds of Formula (I): or a stereoisomer or pharmaceutically acceptable salt form thereof, which are useful as selective inhibitors of serine protease enzymes of the coagulation cascade; for example thrombin, factor Xa, factor XIa, factor IXa, and/or factor VIIa. In particular, it relates to compounds that are factor VIIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same.

  本发明涉及一般用于抑制丝氨酸蛋白酶的化合物。特别是，本发明涉及公式（I）的新型氨基双环吡唑酮和吡啶酮化合物，或其立体异构体或药学上可接受的盐形式，其作为凝血级联反应中的丝氨酸蛋白酶酶类的选择性抑制剂具有用途，例如凝血酶、因子Xa、因子XIa、因子IXa和/或因子VIIa。特别是，本发明涉及因子VIIa抑制剂化合物。本发明还涉及包括这些化合物的制药组合物以及使用它们的方法。
• US7037911B2
  申请人：——

  公开号：US7037911B2

  公开（公告）日：2006-05-02
• Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF–FVIIa inhibitors
  作者：Xiaojun Zhang、Peter W. Glunz、Wen Jiang、Aaron Schmitt、Makenzie Newman、Frank A. Barbera、Jeffery M. Bozarth、Alan R. Rendina、Anzhi Wei、Xiao Wen、Karen A. Rossi、Joseph M. Luettgen、Pancras C. Wong、Robert M. Knabb、Ruth R. Wexler、E. Scott Priestley

  DOI：10.1016/j.bmcl.2013.01.094

  日期：2013.3

  Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF-FVIIa inhibitors. SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups. An Xray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets. Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity. (C) 2013 Elsevier Ltd. All rights reserved.