(S)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide | 625820-83-9

• 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: (S)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide
• 英文别名: LY503430；(S)-4'-(1-(propane-2-sulfonylamino)-2-fluoropropan-2-yl)-N-methylbiphenyl-4-carboxamide；4-[4-[(2S)-2-fluoro-1-(propan-2-ylsulfonylamino)propan-2-yl]phenyl]-N-methylbenzamide
• CAS: 625820-83-9
• 化学式: C₂₀H₂₅FN₂O₃S
• 分子量: 392.495
• InChiKey: MFJKNXILEXBWNQ-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-碘-4-丙-1-烯-2-基苯 在 N-溴代丁二酰亚胺(NBS) 、 四丁基溴化铵 、 potassium carbonate 、 钯 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 乙醇 、 正庚烷 、 二氯甲烷 、 甲基叔丁基醚 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 41.93h， 生成 (S)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide
  参考文献：
  名称：

  Diastereomeric Salt Resolution Based Synthesis of LY503430, an AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Potentiator

  摘要：

  This article describes the development and optimization of chemical reactions and subsequent preparation of the API LY503430 under cGMPs to fund first human dose (FHD) clinical evaluation as a potential therapeutic agent for Parkinson's disease. Reasons and rationale are presented for changes in solvents and reagents. One of the major developments presented here is the replacement of a chiral chromatography with a diastereomeric salt resolution. This article also discusses a preferred orientation issue with LY503430 which complicated the XRPD analysis.

  DOI：

  10.1021/op0500741

文献信息

• Monofluoroalkyl derivatives
  申请人：Eli Lilly and Company

  公开号：US07034045B1

  公开（公告）日：2006-04-25

  The present invention provides certain monofluoroalkyl derivatives useful for potentiating glutamate receptor function in a mammal and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.

  本发明提供了一些单氟代烷基衍生物，这些衍生物可用于增强哺乳动物中的谷氨酸受体功能，因此可用于治疗各种疾病，如精神和神经障碍。
• Enantioselective Synthesis of β-Fluoroamines from β-Amino Alcohols: Application to the Synthesis of LY503430
  作者：Béranger Duthion、Domingo Gomez Pardo、Janine Cossy

  DOI：10.1021/ol1019579

  日期：2010.10.15

  N,N-Dialkyl-β-amino alcohols were enantiospecifically and regioselectively rearranged by using N,N-diethylaminosulfur trifluoride (DAST) to give optically active β-fluoroamines in excellent yields and enantiomeric excesses. This rearrangement was applied to the enantioselective synthesis of LY503430, a potential therapeutic agent for Parkinson’s disease.

  N，N-二烷基-β-氨基醇通过使用N，N-二乙基氨基三氟化硫（DAST）进行对映体和区域选择性重排，从而以优异的收率和过量的对映体得到旋光性β-氟胺。该重排用于LY503430的对映选择性合成，LY503430是帕金森氏病的潜在治疗剂。
• Novel Compounds and Compositions for Treatment of Breathing Control Disorders or Diseases
  申请人：Mannion James C.

  公开号：US20120295911A1

  公开（公告）日：2012-11-22

  The present invention includes compositions that are useful in the treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention.

  本发明包括用于治疗需要呼吸控制疾病或障碍的受体的组合物。本发明还包括一种治疗需要呼吸系统疾病或障碍的受体的方法，包括向受体施用本发明的药物制剂的治疗有效量。本发明还包括一种预防或稳定需要呼吸节律的受体的方法，包括向受体施用本发明的药物制剂的治疗有效量。
• Novel Compounds as Respiratory Stimulants for Treatment of Breathing Control Disorders or Diseases
  申请人：Dax Scott L.

  公开号：US20120142647A1

  公开（公告）日：2012-06-07

  The present invention includes compositions that are useful in the treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention.

  本发明包括用于治疗呼吸控制疾病或障碍的组合物，适用于需要该治疗的受试者。本发明还包括一种治疗呼吸系统疾病或障碍的方法，包括向受试者投予本发明的药物制剂的治疗有效量。本发明还包括一种预防或稳定受试者呼吸节律不稳定的方法，包括向受试者投予本发明的药物制剂的治疗有效量。
• NOVEL COMPOUNDS AND COMPOSITIONS FOR TREATMENT OF BREATHING CONTROL DISORDERS OR DISEASES
  申请人：GALLEON PHARMACEUTICALS, INC.

  公开号：US20140371224A1

  公开（公告）日：2014-12-18

  The present invention includes compounds, and compositions comprising the same, that are useful in the treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention.

  本发明包括化合物及其组合物，适用于治疗需要治疗呼吸控制疾病或障碍的患者。本发明还包括一种治疗需要治疗呼吸系统疾病或障碍的患者的方法，包括向患者施用本发明中化合物的治疗有效量。本发明还包括一种预防或稳定需要稳定呼吸节律的患者的方法，包括向患者施用本发明中化合物的治疗有效量。