3-[bis(tert-butoxycarbonyl)amino]-5-methylpyridine | 1548890-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-[bis(tert-butoxycarbonyl)amino]-5-methylpyridine
• 英文别名: 3-[Bis(tert-butoxycarbonyl)amino]-5-methylpyridine；tert-butyl N-[(2-methylpropan-2-yl)oxycarbonyl]-N-(5-methylpyridin-3-yl)carbamate
• CAS: 1548890-02-3
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: APLQDIGQOCKJSQ-UHFFFAOYSA-N

物化性质

• 沸点：
  394.2±44.0 °C(Predicted)
• 密度：
  1.117±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[bis(tert-butoxycarbonyl)amino]-5-methylpyridine 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 、 四氯化碳 、 mineral oil 为溶剂， 反应 30.25h， 生成 3-((5-aminopyridin-3-yl)methyl)-7-hydroxy-4-methylchromen-2-one
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x
• 作为产物：
  描述：

  3-氨基-5-甲基吡啶 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 20.5h， 生成 3-[bis(tert-butoxycarbonyl)amino]-5-methylpyridine
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x

文献信息

• Bicyclic Pyridazine Compounds as PIM Inhibitors
  申请人：D'amico Derin C.

  公开号：US20140221344A1

  公开（公告）日：2014-08-07

  The invention relates to bicyclic compounds of formulas I and I′, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

  本发明涉及式I和I'的双环化合物及其盐。在某些实施例中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，本发明涉及包含所述化合物的制药组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症方面的应用。
• US9187486B2
  申请人：——

  公开号：US9187486B2

  公开（公告）日：2015-11-17
• Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning
  作者：Toshihiro Aoki、Ikumi Hyohdoh、Noriyuki Furuichi、Sawako Ozawa、Fumio Watanabe、Masayuki Matsushita、Masahiro Sakaitani、Kenji Morikami、Kenji Takanashi、Naoki Harada、Yasushi Tomii、Koji Shiraki、Kentaro Furumoto、Mitsuyasu Tabo、Kiyoshi Yoshinari、Kazutomo Ori、Yuko Aoki、Nobuo Shimma、Hitoshi Iikura

  DOI：10.1021/ml400379x

  日期：2014.4.10

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.