(R)-ethyl 3-(2-bromo-4-fluorophenyl)-3-((S)-(1,1-dimethylethyl)sulfinamido)propanoate | 934346-17-5

• 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: (R)-ethyl 3-(2-bromo-4-fluorophenyl)-3-((S)-(1,1-dimethylethyl)sulfinamido)propanoate
• 英文别名: (β-R)-ethyl 2-bromo-β-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-4-fluorobenzenepropanoate；ethyl (3R)-3-(2-bromo-4-fluorophenyl)-3-[[(S)-tert-butylsulfinyl]amino]propanoate
• CAS: 934346-17-5
• 化学式: C₁₅H₂₁BrFNO₃S
• 分子量: 394.305
• InChiKey: QIKBIBQIBBAYJU-DMZKTXOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-ethyl 3-(2-bromo-4-fluorophenyl)-3-((S)-(1,1-dimethylethyl)sulfinamido)propanoate 在 四氢吡咯 、 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium methylate 、 sodium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 73.5h， 生成 (R)-2-amino-7-[2-(6-ethoxy-pyridin-2-yl)-4-fluoro-phenyl]-4-methyl-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one
  参考文献：
  名称：

  Design, Structure–Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990

  摘要：

  Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

  DOI：

  10.1021/jm501107q
• 作为产物：
  描述：

  2-溴-4-氟苯甲醛 在 titanium(IV) tetraethanolate 、 copper(l) chloride 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 8.83h， 生成 (R)-ethyl 3-(2-bromo-4-fluorophenyl)-3-((S)-(1,1-dimethylethyl)sulfinamido)propanoate
  参考文献：
  名称：

  Design, Structure–Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990

  摘要：

  Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

  DOI：

  10.1021/jm501107q

文献信息

• A Scalable Zinc Activation Procedure Using DIBAL-H in a Reformatsky Reaction
  作者：Michael J. Girgis、Jessica K. Liang、Zhengming Du、Joel Slade、Kapa Prasad

  DOI：10.1021/op900192m

  日期：2009.11.20

  The highly exothermic nature of Reformatsky reagent formation and the reported unpredictability of the induction time for its formation pose challenging problems for scaling up Reformatsky reactions. A zinc-activation procedure using DIBAL-H was developed and investigated using reaction calorimetry along with subsequent parts of the process. This procedure was shown to have important advantages for

  Reformatsky试剂形成的高度放热性质以及所报道的其形成诱导时间的不可预测性为扩大Reformatsky反应规模提出了挑战性的问题。开发了一种使用DIBAL-H的锌活化方法，并使用反应量热法以及该方法的后续步骤进行了研究。与以前的锌活化方法相比，该方法具有扩大规模的重要优势，包括立即通过添加控制的反应立即开始Reformatsky试剂的形成。量热分析在快速指定适合Reformatsky试剂形成的温度时特别有用。该过程已成功扩大规模。
• 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-ones
  申请人：Machajewski D. Timothy

  公开号：US20070123546A1

  公开（公告）日：2007-05-31

  Disclosed are 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Disclosed also are methods of using the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cellular proliferative, viral, autoimmune, cardiovascular, and central nervous system diseases.

  本发明公开了2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物及其立体异构体、互变异构体、药学上可接受的盐和前药；包括药学上可接受的载体和一种或多种2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物的组合物，单独或与至少一种其他治疗剂联合使用的组合物；以及使用2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物，单独或与至少一种其他治疗剂联合使用，在细胞增殖、病毒、自身免疫、心血管和中枢神经系统疾病的预防或治疗中的方法。
• 2-Amino-7,8-dihydro-6H-pyrido[4,3-D]pyrimidin-5-ones
  申请人：Machakewski Timothy D.

  公开号：US20100004237A1

  公开（公告）日：2010-01-07

  Disclosed are 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Disclosed also are methods of using the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cellular proliferative, viral, autoimmune, cardiovascular, and central nervous system diseases.

  本发明涉及2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物及其立体异构体、互变异构体、药学上可接受的盐和前药；包括药学上可接受的载体和一种或多种2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物的组合物，单独使用或与至少一种其他治疗剂联合使用的组合物；以及使用单独使用或与至少一种其他治疗剂联合使用的2-氨基-7,8-二氢-6H-吡啶[4,3-d]嘧啶-5-酮化合物预防或治疗细胞增殖、病毒、自身免疫、心血管和中枢神经系统疾病的方法。
• WO2007/41362
  申请人：——

  公开号：——

  公开（公告）日：——
• US7671059B2
  申请人：——

  公开号：US7671059B2

  公开（公告）日：2010-03-02