methyl (6S)-1-chloro-3-(cyclobutylamino)-4-oxospiro[6,7-dihydropyrrolo[1,2-a]pyrazine-8,1'-cyclopentane]-6-carboxylate | 1426439-83-9

• 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: methyl (6S)-1-chloro-3-(cyclobutylamino)-4-oxospiro[6,7-dihydropyrrolo[1,2-a]pyrazine-8,1'-cyclopentane]-6-carboxylate
• CAS: 1426439-83-9
• 化学式: C₁₇H₂₂ClN₃O₃
• 分子量: 351.833
• InChiKey: NOXQFGNATNUWKX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (6S)-1-chloro-3-(cyclobutylamino)-4-oxospiro[6,7-dihydropyrrolo[1,2-a]pyrazine-8,1'-cyclopentane]-6-carboxylate 、 benzyl ((4-(aminomethyl)phenyl)(imino)methyl)carbamate 在 lithium hydroxide 、 N-甲基吗啉 、 氯甲酸异丁酯 、 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 、 水 、 甲醇 为溶剂， 生成 (6S)-N-[(4-carbamimidoylphenyl)methyl]-1-chloro-3-(cyclobutylamino)-4-oxospiro[6,7-dihydropyrrolo[1,2-a]pyrazine-8,1'-cyclopentane]-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
• 作为产物：
  描述：

  2-O-tert-butyl 3-O-methyl (3S)-1-acetyloxy-2-azaspiro[4.4]nonane-2,3-dicarboxylate 在 三氟化硼乙醚 作用下， 以 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 生成 methyl (6S)-1-chloro-3-(cyclobutylamino)-4-oxospiro[6,7-dihydropyrrolo[1,2-a]pyrazine-8,1'-cyclopentane]-6-carboxylate
  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