2-amino-3-(2-fluorophenyl)propanenitrile | 1011528-03-2

• 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: 2-amino-3-(2-fluorophenyl)propanenitrile
• CAS: 1011528-03-2
• 化学式: C₉H₉FN₂
• 分子量: 164.182
• InChiKey: ZRFUQIFHGWRGFX-UHFFFAOYSA-N

物化性质

• 沸点：
  286.0±30.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-3-(2-fluorophenyl)propanenitrile 在 盐酸 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

  DOI：

  10.1021/acs.jmedchem.7b00449
• 作为产物：
  描述：

  2-氟溴苄 在 盐酸 、 potassium tert-butylate 、 四丁基碘化铵 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 生成 2-amino-3-(2-fluorophenyl)propanenitrile
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

  DOI：

  10.1021/acs.jmedchem.7b00449

文献信息

• PYRAZOLOPYRIDINE, INDAZOLE, IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE, PYRAZOLOPYRAZINE AND PYRAZOLOPYRIDINE DERIVATIVES AS STIMULATORS OF GUANYLATE CYCLASE FOR CARDIOVASCULAR DISORDERS
  申请人：Schirok Hartmut

  公开号：US20100029653A1

  公开（公告）日：2010-02-04

  The present application relates to novel azabicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and/or prevention of diseases, and their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

  本申请涉及新型氮杂双环化合物，其制备方法，它们单独或与其他物质结合用于治疗和/或预防疾病，以及用于生产治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管疾病。
• Flow Synthesis of Fluorinated α-Amino Acids
  作者：Stella Vukelić、Dmitry B. Ushakov、Kerry Gilmore、Beate Koksch、Peter H. Seeberger

  DOI：10.1002/ejoc.201500300

  日期：2015.5

  semi-continuous process for the synthesis of racemic fluorinated α-amino acids from fluorinated amines is described. Following a singlet-oxygen-driven photooxidative cyanation, an acid-mediated hydrolysis of the intermediate α-amino nitrile yields the desired α-amino acid. Aliphatic, benzylic, and homobenzylic residues with different fluorination degrees are tolerated, providing good overall yields (50–67 %). This

  氟化 α-氨基酸是用途广泛的化合物，可用于医学和生物化学的多种用途。然而，它们的合成仍然是一个重大障碍，通常需要多个步骤、多个保护基团和/或使用剧毒试剂。这些挑战限制了氟化α-氨基酸的应用。描述了一种从氟化胺合成外消旋氟化 α-氨基酸的方便、无保护基团和半连续的方法。在单线态氧驱动的光氧化氰化作用之后，中间体 α-氨基腈的酸介导水解产生所需的 α-氨基酸。可以耐受具有不同氟化度的脂肪族、苄基和高苄基残基，提供良好的总产率 (50–67%)。
• Pyrazolopyridine, indazole, imidazopyridine, imidazopyrimidine, pyrazolopyrazine and pyrazolopyridine derivatives as stimulators of guanylate cyclase for cardiovascular disorders
  申请人：Bayer Intellectual Property GmbH

  公开号：US08309551B2

  公开（公告）日：2012-11-13

  The present application relates to novel azabicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and/or prevention of diseases, and their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

  本申请涉及新型杂环双环化合物、其制备过程，它们单独或组合使用用于治疗和/或预防疾病，以及它们用于制造治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管疾病。
• PYRAZOLOPYRIDIN, INDAZOL, IMIDAZOPYRIDIN, IMIDAZOPYRIMIDIN, PYRAZOLOPYRAZIN UND PYRAZOLOPYRIDIN DERIVATE ALS STIMULATOREN DER GUANYLATCYCLASE ZUR HERZ-KREISLAUFERKRANKUNGEN
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2066666A1

  公开（公告）日：2009-06-10
• US8309551B2
  申请人：——

  公开号：US8309551B2

  公开（公告）日：2012-11-13