tert-butyl (3S)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate | 1610536-43-0

• 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 (3S)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate
• 英文别名: tert-butyl (3S)-4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylate
• CAS: 1610536-43-0
• 化学式: C₁₆H₂₂N₄O₂
• 分子量: 302.376
• InChiKey: NWIJUURQIDKJEO-LBPRGKRZSA-N

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 (3S)-4-(5-cyano-2-pyridyl)-3-methylpiperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 6-[(2S)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile
  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 、 (S)-4-N-叔丁氧羰基-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 (3S)-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

• Poly-ADP ribose polymerase (PARP) inhibitors
  申请人：Mitobridge, Inc.

  公开号：US11034670B2

  公开（公告）日：2021-06-15

  The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.

  本发明涉及一种药物组合物，该组合物包含一种药学上可接受的载体或稀释剂和一种由以下结构式表示的化合物： 本发明还涉及一种治疗患有可通过抑制聚（ADP-核糖）聚合酶（PARP）而改善的疾病的受试者的方法。本文提供了变量的定义。
• WO2018125961A5
  申请人：——

  公开号：WO2018125961A5

  公开（公告）日：2022-04-19
• POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
  申请人：Mitobridge, Inc.

  公开号：US20200071299A1

  公开（公告）日：2020-03-05

  The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
• [EN] POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS<br/>[FR] INHIBITEURS DE LA POLY-ADP-RIBOSE POLYMÉRASE (PARP)
  申请人：MITOBRIDGE INC

  公开号：WO2018125961A1

  公开（公告）日：2018-07-05

  The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
• 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.