(S)-N-(3-(2-amino-4-oxopentan-2-yl)-4-fluorophenyl)-2,2,2-trifluoroacetamide | 1310877-30-5

• 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)-N-(3-(2-amino-4-oxopentan-2-yl)-4-fluorophenyl)-2,2,2-trifluoroacetamide
• 英文别名: N-[3-[(2S)-2-amino-4-oxopentan-2-yl]-4-fluorophenyl]-2,2,2-trifluoroacetamide
• CAS: 1310877-30-5
• 化学式: C₁₃H₁₄F₄N₂O₂
• 分子量: 306.26
• InChiKey: ZCSZTHXSKDOJIO-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-(3-(2-amino-4-oxopentan-2-yl)-4-fluorophenyl)-2,2,2-trifluoroacetamide 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 41.0h， 生成 C₃₃H₃₇F₄N₃O₆S
  参考文献：
  名称：

  OXAZINE DERIVATIVES

  摘要：

  本发明提供了一种如下所述的化合物作为治疗或预防由淀粉样蛋白-β的产生、分泌或沉积引起的疾病的药物。式(I)的化合物：其中R1、R2a、R2b、R3、R4a、R4b、环A和虚线在说明书中有定义，其药用可接受的盐或其溶剂化合物。

  公开号：

  US20120245157A1
• 作为产物：
  描述：

  1-(2-氟-5-硝基苯基)乙-1-酮 在 盐酸 、 titanium(IV) tetraethanolate 、 铁粉 、 氯化铵 、 臭氧 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 17.67h， 生成 (S)-N-(3-(2-amino-4-oxopentan-2-yl)-4-fluorophenyl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  Rational Design of Novel 1,3-Oxazine Based β-Secretase (BACE1) Inhibitors: Incorporation of a Double Bond To Reduce P-gp Efflux Leading to Robust Aβ Reduction in the Brain

  摘要：

  Accumulation of A beta peptides is a hallmark of Alzheimer's disease (AD) and is considered a causal factor in the pathogenesis of AD. beta-Secretase (BACE1) is a key enzyme responsible for producing A beta peptides, and thus agents that inhibit BACE1 should be beneficial for disease-modifying treatment of AD. Here we describe the discovery and optimization of novel oxazine-based BACE1 inhibitors by lowering amidine basicity with the incorporation of a double bond to improve brain penetration. Starting from a 1,3-dihydrooxazine lead 6 identified by a hit-to-lead SAR following HTS, we adopted a pKa lowering strategy to reduce the P-gp efflux and the high hERG potential leading to the discovery of 15 that produced significant A beta reduction with long duration in pharmacodynamic models and exhibited wide safety margins in cardiovascular safety models. This compound improved the brain-to-plasma ratio relative to 6 by reducing P-gp recognition, which was demonstrated by a P-gp knockout mouse model.

  DOI：

  10.1021/acs.jmedchem.8b00002

文献信息

• FUSED AMINODIHYDROPYRIMIDINE DERIVATIVE
  申请人：Masui Moriyasu

  公开号：US20130210839A1

  公开（公告）日：2013-08-15

  The present invention provides, for example, the following compound: wherein ring A is a substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, X 1 —X 2 ═X 3 is CR 5 —CR 6 ═CR 7 , N—CR 6 ═CR 7 , CR 5 —N═CR 7 or CR 5 —CR 6 ═N, R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or the like, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted alkyl or the like, R 4a , R 4b , R 5 , R 6 and R 7 are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl or the like, its pharmaceutically acceptable salt or a solvate thereof having an effect of inhibiting amyloid β production, especially a BACE1 inhibitory activity, and useful as a medicament for treating diseases induced by production, secretion or deposition of amyloid β proteins.

  本发明提供了如下化合物：其中环A是取代或未取代的碳环或取代或未取代的杂环，X1—X2═X3为CR5—CR6═CR7，N—CR6═CR7，CR5—N═CR7或CR5—CR6═N，R1为取代或未取代的烷基，取代或未取代的烯基等，R2a和R2b各自独立为氢，取代或未取代的烷基等，R4a，R4b，R5，R6和R7各自独立为氢，卤素，羟基，取代或未取代的烷基等，其药学上可接受的盐或其溶剂化合物具有抑制淀粉样蛋白β产生的作用，特别是BACE1抑制活性，并可用作治疗由淀粉样蛋白β蛋白产生、分泌或沉积引起的疾病的药物。
• Facile Construction of an Amino-1,3-Oxazine Scaffold using Burgess Reagent Under Mild Conditions
  作者：Kouki Fuchino、Moriyasu Masui、Shuhei Yoshida、Ken-ichi Kusakabe

  DOI：10.1016/j.tetlet.2020.152684

  日期：2021.2

  The development of a cyclization reaction to access amino-1,3-oxazines under mild conditions is described. The synthesis was achieved using dehydrating reagents, such as phosphorus pentoxide and Burgess reagent. In particular, the cyclization with Burgess reagent proceeded under mild conditions and tolerated potentially labile functional groups, such as the acetoxy group, and therefore can be used

  描述了在温和条件下获得氨基-1,3-恶嗪环化反应的进展。使用脱水剂如五氧化二磷和Burgess试剂可完成合成。特别是，使用Burgess试剂的环化反应在温和的条件下进行，并且可以耐受潜在不稳定的官能团（如乙酰氧基），因此可用于合成具有多种氨基-1,3-恶嗪的β-分泌酶（BACE1）抑制剂弹头。
• OXAZINE DERIVATIVE
  申请人：Shionogi & Co., Ltd.

  公开号：EP2511268A1

  公开（公告）日：2012-10-17

  The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-β proteins. A compound of the formula (I): wherein R1, R2a, R2b, R3, R4a, R4b, ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.

  本发明提供了例如下述化合物，作为治疗或预防由淀粉样β蛋白的产生、分泌或沉积诱发的疾病的药物。 式 (I) 的化合物： 其中 R1、R2a、R2b、R3、R4a、R4b、环 A 和虚线的定义见说明书、 其药学上可接受的盐或其溶液。
• US9018219B2
  申请人：——

  公开号：US9018219B2

  公开（公告）日：2015-04-28
• US8999980B2
  申请人：——

  公开号：US8999980B2

  公开（公告）日：2015-04-07