trans-(2S,3S)-dimethylmorpholine hydrochloride | 316806-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: trans-(2S,3S)-dimethylmorpholine hydrochloride
• 英文别名: (2S,3S)-2,3-dimethylmorpholine hydrochloride；(2S,3S)-2,3-dimethylmorpholine;hydrochloride
• CAS: 316806-96-9
• 化学式: C₆H₁₃NO*ClH
• 分子量: 151.636
• InChiKey: KZWKLXAWHKRNQF-GEMLJDPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-6-(3-fluoropyridin-4-yl)-3-methylpyrimidin-4(3H)-one 、 trans-(2S,3S)-dimethylmorpholine hydrochloride 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-[(2S,3S)-2,3-dimethylmorpholin-4-yl]-6-(3-fluoropyridin-4-yl)-3-methylpyrimidin-4-one
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005
• 作为产物：
  描述：

  在 锂硼氢 、 三甲基氯硅烷 、 1-氯乙基氯甲酸酯 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 7.0h， 生成 trans-(2S,3S)-dimethylmorpholine hydrochloride
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005

文献信息

• Synthesis and Antitumor Activity of Benzimidazolyl-1,3,5-triazine and Benzimidazolylpyrimidine Derivatives.
  作者：Toshiyuki MATSUNO、Masanobu KATO、Hiroya SASAHARA、Tetsuo WATANABE、Masahiro INABA、Masayuki TAKAHASHI、Shin-ichi YAGUCHI、Kimitomo YOSHIOKA、Mitsuo SAKATO、Seiichiro KAWASHIMA

  DOI：10.1248/cpb.48.1778

  日期：——

  Triamino-substituted 1, 3, 5-triazine and pyrimidine derivatives were synthesized and tested for antimtuor activities using some human cancer cell lines and murine leukemia cell lines. All the compounds having benzimidazolyl and morpholino groups as substituents on the 1, 3, 5-traizine ring showed antitumor activity. Pyrimidine derivatives having the same groups as substituents also showed antitumor activity. Among them, the compounds having 1-benzimidazolyl, morpholino and cis-2, 3-dimethylmorpholino groups as substituents on the 1, 3, 5-triazine ring or pyrimidine ring exhibited the most potent antitumor activity, and these compounds exhibited no or very weak aromatase inhibitory activity. In contrast, the compounds having imidazolyl group instead of benzimidazolyl group as a substituent on the 1, 3, 5-triazine ring showed a potent aromatase inhibitory activity.

  研究人员合成了三氨基取代的 1, 3, 5-三嗪和嘧啶衍生物，并利用一些人类癌症细胞系和小鼠白血病细胞系对其抗肿瘤活性进行了测试。所有在 1，3，5-三嗪环上具有苯并咪唑基和吗啉基取代基的化合物都显示出抗肿瘤活性。具有相同取代基团的嘧啶衍生物也具有抗肿瘤活性。其中，以 1，3，5-三嗪环或嘧啶环上的 1-苯并咪唑基、吗啉基和顺式-2，3-二甲基吗啉基为取代基的化合物表现出最强的抗肿瘤活性，这些化合物不表现出或表现出很弱的芳香化酶抑制活性。与此相反，在 1，3，5-三嗪环上以咪唑基取代苯并咪唑基的化合物具有很强的芳香化酶抑制活性。
• 2,6,7,8 SUBSTITUTED PURINES AS HDM2 INHIBITORS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20150353553A1

  公开（公告）日：2015-12-10

  The present invention provides 2,6,7,8 Substituted Purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.

  本发明提供了如本文所述的2,6,7,8取代嘌呤或其药学上可接受的盐。这些代表性化合物可用作HDM2蛋白的抑制剂。本发明还公开了包含上述化合物的药物组合物以及使用它们治疗癌症的潜在方法。
• US9540377B2
  申请人：——

  公开号：US9540377B2

  公开（公告）日：2017-01-10