(3S,7R,8aS)-3-methyloctahydropyrrolo[1,2-a]pyrazine-7-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (3S,7R,8aS)-3-methyloctahydropyrrolo[1,2-a]pyrazine-7-ol
• 英文别名: (3S,7R,8AS)-3-methyloctahydropyrrolo-[1,2-a]pyrazin-7-ol；(3S,7R,8aS)-3-methyl-1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazin-7-ol
• 化学式: C₈H₁₆N₂O
• 分子量: 156.228
• InChiKey: XQEKTFPFYZIXMT-BIIVOSGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  {3-[4-(4-butyryl-5-methylpyrazol-1-yl)phenylcarbamoyl]-5-methylindol-1-yl}acetic acid 、 (3S,7R,8aS)-3-methyloctahydropyrrolo[1,2-a]pyrazine-7-ol 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 、 盐酸 作用下， 以 二氯甲烷 、 乙醚 、 丙酮 为溶剂， 以28%的产率得到[4-(4-butyryl-5-methyl-pyrazol-1-yl)phenyl]-1-[2-((3S,7R,8aS)-7-hydroxy-3-methylhexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-2-oxoethyl]-5-methyl-1H-indole-3-carboxamide hydrochloride
  参考文献：
  名称：

  N-[6-(4-Butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

  摘要：

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

  DOI：

  10.1021/jm500588w
• 作为产物：
  描述：

  (2'S,4'R)-methyl 1'-((S)-2-tert-butoxycarbonyl)aminopropanoyl-4'-hydroxypyrrolidine-2'-carboxylate 在 sodium tetrahydroborate 、 碘 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (3S,7R,8aS)-3-methyloctahydropyrrolo[1,2-a]pyrazine-7-ol
  参考文献：
  名称：

  Enantiomerically pure piperazines via NaBH4/I2 reduction of cyclic amides

  摘要：

  Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (35,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2016.12.002

文献信息

• <i>N</i>-[6-(4-Butanoyl-5-methyl-1<i>H</i>-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1<i>H</i>-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist
  作者：Christophe Boldron、Angélina Besse、Marie-Françoise Bordes、Stéphanie Tissandié、Xavier Yvon、Benjamin Gau、Alain Badorc、Tristan Rousseaux、Guillaume Barré、Jérôme Meneyrol、Gernot Zech、Marc Nazare、Valérie Fossey、Anne-Marie Pflieger、Sandrine Bonnet-Lignon、Laurence Millet、Christophe Briot、Frédérique Dol、Jean-Pascal Hérault、Pierre Savi、Gilbert Lassalle、Nathalie Delesque、Jean-Marc Herbert、Françoise Bono

  DOI：10.1021/jm500588w

  日期：2014.9.11

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.
• Enantiomerically pure piperazines via NaBH4/I2 reduction of cyclic amides
  作者：Vagala Harish、Mariappan Periasamy

  DOI：10.1016/j.tetasy.2016.12.002

  日期：2017.1

  Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (35,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine. (C) 2016 Elsevier Ltd. All rights reserved.