tert-butyl (3R)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate | 912556-68-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl (3R)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate
• 英文别名: tert-butyl (3R)-4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylate；Tert-butyl (3r)-4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylate
• CAS: 912556-68-4
• 化学式: C₁₆H₂₂N₄O₂
• 分子量: 302.376
• InChiKey: NWIJUURQIDKJEO-GFCCVEGCSA-N

物化性质

• 沸点：
  461.3±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 19.5h， 生成 (R)-6-(4-(4-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
  参考文献：
  名称：

  Orally Active 7-Substituted (4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as Active-Site Inhibitors of Sphingosine 1-Phosphate Lyase for the Treatment of Multiple Sclerosis

  摘要：

  Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases.

  DOI：

  10.1021/jm500338n
• 作为产物：
  描述：

  6-氯-3-氰基吡啶 、 (R)-4-Boc-2-甲基哌嗪 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 tert-butyl (3R)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Orally Active 7-Substituted (4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as Active-Site Inhibitors of Sphingosine 1-Phosphate Lyase for the Treatment of Multiple Sclerosis

  摘要：

  Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases.

  DOI：

  10.1021/jm500338n

文献信息

• Novel compounds of amino sulfonyl derivatives
  申请人：Cheng Hengmiao

  公开号：US20070027118A1

  公开（公告）日：2007-02-01

  The present invention relates to compounds with formula (I) or a pharmaceutically acceptable salt thereof: wherein; T is a (4 to 10)-membered heterocyclyl and wherein R 1 , R 2 and R 3 are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of the 11-β-hsd-1 enzyme.

  本发明涉及具有公式（I）或其药学上可接受的盐的化合物：其中；T是（4至10）成员的杂环基，其中R1，R2和R3如规范中所定义。本发明还涉及包含公式（I）化合物的药物组合物以及治疗通过调节11-β-hsd-1酶介导的疾病的方法。
• WO2018125961A5
  申请人：——

  公开号：WO2018125961A5

  公开（公告）日：2022-04-19
• [EN] AMINO SULFONYL DERIVATIVES AS INHIBITORS OF HUMAN 11-.BETA.-HYDROSYSTEROID DEHYDROGENASE<br/>[FR] NOUVEAUX COMPOSES DE DERIVES AMINOSULFONYLES
  申请人：PFIZER

  公开号：WO2006106423A3

  公开（公告）日：2007-01-04
• Orally Active 7-Substituted (4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as Active-Site Inhibitors of Sphingosine 1-Phosphate Lyase for the Treatment of Multiple Sclerosis
  作者：Sven Weiler、Nadine Braendlin、Christian Beerli、Christian Bergsdorf、Anna Schubart、Honnappa Srinivas、Berndt Oberhauser、Andreas Billich

  DOI：10.1021/jm500338n

  日期：2014.6.26

  Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases.