(6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl ester | 639831-08-6

• 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: (6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl ester
• 英文别名: (6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic Acid Benzyl Ester；benzyl N-[(6S)-4-oxo-6-(phenylcarbamoyl)-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidin-3-yl]-N-prop-2-enylcarbamate
• CAS: 639831-08-6
• 化学式: C₂₅H₂₄N₄O₄
• 分子量: 444.49
• InChiKey: AYXRGFFABHVMCP-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl ester 在 4-二甲氨基吡啶 、 碳酸二叔丁酯 、 lithium hexamethyldisilazane 作用下， 生成 (6S)-4-oxo-3-[phenylmethoxycarbonyl(prop-2-enyl)amino]-8,8-dipropyl-6,7-dihydropyrrolo[1,2-a]pyrimidine-6-carboxylic acid
  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
• 作为产物：
  描述：

  (6S)-3-(allyl-benzyloxycarbonyl-amino)-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidine-6-carboxylic acid 、 苯胺 在 N-羟基-7-氮杂苯并三氮唑 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 (6S)-allyl-(4-oxo-6-phenylcarbamoyl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl)-carbamic acid benzyl ester
  参考文献：
  名称：

  Bicyclic pyrimidinones as coagulation cascade inhibitors

  摘要：

  本发明一般涉及抑制丝氨酸蛋白酶的化合物。具体而言，本发明涉及式（I）的新型氨基双环嘧啶酮化合物或其立体异构体或药学上可接受的盐形式，这些化合物可用作凝血级联中丝氨酸蛋白酶的选择性抑制剂；例如凝血酶、X因子a、XI因子a、IX因子a和/或VII因子a。特别是，涉及抑制VII因子a的化合物。本发明还涉及包含这些化合物的药物组合物以及使用相同的方法。

  公开号：

  US20040006065A1

文献信息

• US7094783B2
  申请人：——

  公开号：US7094783B2

  公开（公告）日：2006-08-22
• Bicyclic pyrimidinones as coagulation cascade inhibitors
  申请人：——

  公开号：US20040006065A1

  公开（公告）日：2004-01-08

  The present invention relates generally to compounds that inhibit serine proteases. In particular it is directed to novel amino-bicyclic pyrimidinone compounds of Formula (I): 1 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.

  本发明一般涉及抑制丝氨酸蛋白酶的化合物。具体而言，本发明涉及式（I）的新型氨基双环嘧啶酮化合物或其立体异构体或药学上可接受的盐形式，这些化合物可用作凝血级联中丝氨酸蛋白酶的选择性抑制剂；例如凝血酶、X因子a、XI因子a、IX因子a和/或VII因子a。特别是，涉及抑制VII因子a的化合物。本发明还涉及包含这些化合物的药物组合物以及使用相同的方法。
• 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.