(S)-1-aminooxy-propan-2-ol | 739355-10-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-1-aminooxy-propan-2-ol
• 英文别名: (2S)-1-aminooxypropan-2-ol
• CAS: 739355-10-3
• 化学式: C₃H₉NO₂
• 分子量: 91.11
• InChiKey: NDJYVTLJWDGQGL-VKHMYHEASA-N

物化性质

• 沸点：
  216.1±23.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  6
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对硝基苯磺酰氯 、 (S)-1-aminooxy-propan-2-ol 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 4.17h， 以1.31 g的产率得到C₉H₁₂N₂O₆S
  参考文献：
  名称：

  1,2-氧氮杂环丁烷的环-应变使能催化不对称Umpolung CO键形成反应，用于合成功能性手性醚。

  摘要：

  在手性相转移催化剂的存在下，N-烷基1,2-氧氮杂环丁烷与β-酮酯的空前催化不对称C-O键形成催化反应已经实现，从而可以使用一系列高度官能化的手性醚具有四元且没有相邻的立体发生中心，具有高产率，出色的对映选择性和非对映选择性（高达97％ee和20：1 dr）。这些多功能产品可以通过两个步骤灵活地转变为生物学上重要的手性融合和螺吗啉。

  DOI：

  10.1021/acs.orglett.0c01916
• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (S)-1-aminooxy-propan-2-ol
  参考文献：
  名称：

  1,2-氧氮杂环丁烷的环-应变使能催化不对称Umpolung CO键形成反应，用于合成功能性手性醚。

  摘要：

  在手性相转移催化剂的存在下，N-烷基1,2-氧氮杂环丁烷与β-酮酯的空前催化不对称C-O键形成催化反应已经实现，从而可以使用一系列高度官能化的手性醚具有四元且没有相邻的立体发生中心，具有高产率，出色的对映选择性和非对映选择性（高达97％ee和20：1 dr）。这些多功能产品可以通过两个步骤灵活地转变为生物学上重要的手性融合和螺吗啉。

  DOI：

  10.1021/acs.orglett.0c01916

文献信息

• BICYCLIC HETEROCYCLES AS MEK KINASE INHIBITORS
  申请人：Heald Robert Andrew

  公开号：US20110190257A1

  公开（公告）日：2011-08-04

  The invention relates to bicyclic heterocycles of formulae I and II with anti-cancer and/or anti-inflammatory activity and more specifically with MEK kinase inhibitory activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth, treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  本发明涉及公式I和II的双环杂环化合物，具有抗癌和/或抗炎活性，更具体地具有MEK激酶抑制活性。本发明提供了用于抑制异常细胞生长、治疗增生性疾病或治疗哺乳动物的炎症性疾病的组合物和方法。本发明还涉及使用这些化合物进行哺乳动物细胞的体外、体内诊断或治疗，或相关病理条件的方法。
• Bicyclic heterocycles as MEK kinase inhibitors
  申请人：Heald Robert A.

  公开号：US08841462B2

  公开（公告）日：2014-09-23

  The invention relates to bicyclic heterocycles of formulae I and II with anti-cancer and/or anti-inflammatory activity and more specifically with MEK kinase inhibitory activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth, treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  本发明涉及公式I和II的双环杂环化合物，具有抗癌和/或抗炎活性，更具有MEK激酶抑制活性。本发明提供了用于抑制异常细胞生长、治疗过度增殖性疾病或治疗哺乳动物的炎症性疾病的组合物和方法。本发明还涉及使用该化合物进行哺乳动物细胞的体外、原位和体内诊断或治疗，或相关病理条件的方法。
• Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479
  作者：Kirk D. Robarge、Wendy Lee、Charles Eigenbrot、Mark Ultsch、Christian Wiesmann、Robert Heald、Steve Price、Joanne Hewitt、Philip Jackson、Pascal Savy、Brenda Burton、Edna F. Choo、Jodie Pang、Jason Boggs、April Yang、Xioaye Yang、Matthew Baumgardner

  DOI：10.1016/j.bmcl.2014.08.008

  日期：2014.10

  Use of the tools of SBDD including crystallography led to the discovery of novel and potent 6,5 heterobicyclic MEKi's [J. Med. Chem. 2012, 55, 4594]. The core change from a 5,6 heterobicycle to a 6,5 heterobicycle was driven by the desire for increased structural diversity and aided by the co-crystal structure of G-925 [J. Med. Chem. 2012, 55, 4594]. The key design feature was the shift of the attachment of the five-membered heterocyclic ring towards the B ring while maintaining the key hydroxamate and anilino pharamcophoric elements in a remarkably similar position as in G-925. From modelling, changing the connection point of the five membered ring heterocycle placed the H-bond accepting nitrogen within a good distance and angle to the Ser212 [J. Med. Chem. 2012, 55, 4594]. The resulting novel 6,5 benzoisothiazole MEKi G-155 exhibited improved potency versus aza-benzofurans G-925 and G-963 but was a potent inhibitor of cytochrome P450's 2C9 and 2C19. Lowering the logD by switching to the more polar imidazo[1,5-a] pyridine core significantly diminished 2C9/2C19 inhibition while retaining potency. The imidazo[1,5-a] pyridine G-868 exhibited increased potency versus the starting point for this work (azabenzofuran G-925) leading to deprioritization of the azabenzofurans. The 6,5-imidazo[1,5-a] pyridine scaffold was further diversified by incorporating a nitrogen at the 7 position to give the imidazo[1,5-a] pyrazine scaffold. The introduction of the C7 nitrogen was driven by the desire to improve metabolic stability by blocking metabolism at the C7 and C8 positions (particularly the HLM stability). It was found that improving on G-868 (later renamed GDC-0623) required combining C7 nitrogen with a diol hydroxamate to give G-479. G-479 with polarity distributed throughout the molecule was improved over G-868 in many aspects. (C) 2014 Elsevier Ltd. All rights reserved.