(S)-2-(pyrrolidin-2-yl)acetonitrile | 1186242-37-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-2-(pyrrolidin-2-yl)acetonitrile
• 英文别名: (S)-Pyrrolidin-2-yl-acetonitrile；2-[(2S)-pyrrolidin-2-yl]acetonitrile
• CAS: 1186242-37-4
• 化学式: C₆H₁₀N₂
• 分子量: 110.159
• InChiKey: LDOZNMLVJHQCAB-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-(pyrrolidin-2-yl)acetonitrile 在 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 5.5h， 生成 (S)-2-(1-(2-((1-benzylpiperidin-4-yl)(methyl)amino)thieno[3,2-d]pyrimidin-4-yl)pyrrolidin-2-yl)acetonitrile
  参考文献：
  名称：

  Novel Thienopyrimidine Inhibitors of Leishmania N-Myristoyltransferase with On-Target Activity in Intracellular Amastigotes

  摘要：

  The leishmaniases, caused by Leishmania species of protozoan parasites, are neglected tropical diseases with millions of cases worldwide. Current therapeutic approaches are limited by toxicity, resistance, and cost. N-Myristoyltransferase (NMT), an enzyme ubiquitous and essential in all eukaryotes, has been validated via genetic and pharmacological methods as a promising anti- leishmanial target. Here we describe a comprehensive structure-activity relationship (SAR) study of a thienopyrimidine series previously identified in a high-throughput screen against Leishmania NMT, across 68 compounds in enzyme- and cell-based assay formats. Using a chemical tagging target engagement biomarker assay, we identify the first inhibitor in this series with on-target NMT activity in leishmania parasites. Furthermore, crystal structure analyses of 12 derivatives in complex with Leishmania major NMT revealed key factors important for future structure-guided optimization delivering IMP-105 (43), a compound with modest activity against Leishmania donovani intracellular amastigotes and excellent selectivity (>660-fold) for Leishmania NMT over human NMTs.

  DOI：

  10.1021/acs.jmedchem.0c00570
• 作为产物：
  描述：

  (S)-tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-3-one 在 potassium cyanide 、 18-冠醚-6 作用下， 反应 7.0h， 以65%的产率得到(S)-2-(pyrrolidin-2-yl)acetonitrile
  参考文献：
  名称：

  由2-恶唑烷酮与氰化物离子开环合成3-氨基丙腈的新方法

  摘要：

  在18-冠-6存在下，氰离子对2-恶唑烷酮的5-位的亲核攻击产生了3-氨基丙腈。

  DOI：

  10.1016/j.tetlet.2009.06.014

文献信息

• [EN] METHODS OF TREATING LIVER DISEASES<br/>[FR] MÉTHODES DE TRAITEMENT DE MALADIES HÉPATIQUES
  申请人：ZAFGEN INC

  公开号：WO2014071368A1

  公开（公告）日：2014-05-08

  The invention provides tricyclic compounds and their use in treating liver disorders, such as non-alcoholic steatohepatitis and related disorders (e.g., fibrosis). The compounds are contemplated to have activity against methionyl aminopeptidase 2.

  这项发明提供了三环化合物及其在治疗肝病方面的用途，如非酒精性脂肪性肝炎和相关疾病（如纤维化）。这些化合物被认为具有对蛋氨酸氨肽酶2的活性。
• Partially Saturated Tricyclic Compounds and Methods of Making and Using Same
  申请人：Cramp Susan Mary

  公开号：US20140088078A1

  公开（公告）日：2014-03-27

  The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

  本发明提供了三环化合物及其在治疗医学疾病，如肥胖症中的应用。同时提供了制备各种三环化合物的药物组合物和方法。这些化合物被认为对甲硫氨酰基氨肽酶2具有活性。
• METHODS OF TREATING LIVER DISEASES
  申请人：ZAFGEN, INC.

  公开号：US20160058731A1

  公开（公告）日：2016-03-03

  The invention provides tricyclic compounds and their use in treating liver disorders, such as non-alcoholic steatohepatitis and related disorders (e.g., fibrosis). The compounds are contemplated to have activity against methionyl aminopeptidase 2.

  该发明提供了三环化合物及其在治疗肝脏疾病，如非酒精性脂肪性肝炎及相关疾病（例如纤维化）方面的用途。这些化合物被认为具有对甲硫氨酰基肽酶2的活性。
• [EN] PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME<br/>[FR] COMPOSÉS TRICYCLIQUES PARTIELLEMENT SATURÉS ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：ZAFGEN INC

  公开号：WO2012154676A9

  公开（公告）日：2014-03-27
• PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
  申请人：Zafgen, Inc.

  公开号：EP2705030B1

  公开（公告）日：2016-07-27