2-methyl-10-(4-methyl-piperazinyl)-4-prop-2-ynyl-4H-3-thia-4,9-diaza-benzo[f]azulene | 155817-87-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-methyl-10-(4-methyl-piperazinyl)-4-prop-2-ynyl-4H-3-thia-4,9-diaza-benzo[f]azulene
• 英文别名: 2-Methyl-4-(4-methyl-1-piperazinyl)-10-(prop-2-ynyl)-10H-thieno[2,3-b][1,5]benzodiazepine；2-Methyl-4-(4-methylpiperazin-1-yl)-10-prop-2-ynylthieno[2,3-b][1,5]benzodiazepine
• CAS: 155817-87-1
• 化学式: C₂₀H₂₂N₄S
• 分子量: 350.487
• InChiKey: KTEXQPWZUCHZPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  50.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-10-(4-methyl-piperazinyl)-4-prop-2-ynyl-4H-3-thia-4,9-diaza-benzo[f]azulene 、 4-叠氮基丁酸乙酯 在 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以87%的产率得到
  参考文献：
  名称：

  1,2,3-Triazoles derived from olanzapine: their synthesis via an ultrasound assisted CuAAC method and evaluation as inhibitors of PDE4B

  摘要：

  一种超声波辅助的CuAAC方法提供了从奥兰扎平衍生的新型1,2,3-三唑作为PDE4B的抑制剂。

  DOI：

  10.1039/c5ra20380e
• 作为产物：
  描述：

  3-溴丙炔 、 奥氮平 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 以87%的产率得到2-methyl-10-(4-methyl-piperazinyl)-4-prop-2-ynyl-4H-3-thia-4,9-diaza-benzo[f]azulene
  参考文献：
  名称：

  Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

  摘要：

  描述了一种将抗精神病药物奥氮平转化为PDE4抑制剂的新策略，通过设计和Pd/C介导合成新型N-吲哚基甲基奥氮平衍生物。一种化合物表现出良好的抑制作用（IC50 1.1 μM），并且对PDE4B的选择性超过PDE4D超过10倍，这得到了对接研究的支持。该化合物还显示出显著抑制TNF-α，并且在细胞系和斑马鱼胚胎模型中没有明显的毒性，除了在啮齿动物中需要重新评估的致畸效应。

  DOI：

  10.1039/c3ob27424a

文献信息

• Thienobenzodiazepine derivatives for treatment of CNS disorders
  申请人：LILLY INDUSTRIES LIMITED

  公开号：EP0582368A1

  公开（公告）日：1994-02-09

  Pharmaceutical compounds of the formula in which R¹ is hydrogen or halo, and R² is C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₆ cycloalkyl optionally substituted by 1 to 3 C₁₋₄ alkyl groups, C₃₋₆ cycloalkyl-C₁₋₄ alkyl in which the cycloalkyl group is optionally substituted by 1 to 3 C₁₋₄ alkyl groups, or optionally substituted phenyl-C₁₋₄ alkyl; or a salt thereof.

  式中的药物化合物 其中 R¹ 为氢或卤代，R² 为 C₁₋₁₀烷基、C₂₋₁₀ 烯基、C₂₋₁₀ 炔基、C₃₋₆环烷基，可任选被 1 至 3 个 C₁₋₄ 烷基取代、C₃₋₆环烷基-₁₋₄ 烷基，其中环烷基任选被 1 至 3 个 C₁₋₄ 烷基取代，或任选被苯基-₁₋₄ 烷基取代；或其盐。
• Synthesis of N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B
  作者：P. Vijaya Babu、Dhilli Rao Gorja、Chandana Lakshmi T. Meda、Girdhar Singh Deora、Sunder Kumar Kolli、Kishore V.L. Parsa、K. Mukkanti、Manojit Pal

  DOI：10.1016/j.tetlet.2014.04.009

  日期：2014.5

  The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated C-C bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies. (C) 2014 Elsevier Ltd. All rights reserved.
• US6034078A
  申请人：——

  公开号：US6034078A

  公开（公告）日：2000-03-07
• Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors
  作者：Dhilli Rao Gorja、Soumita Mukherjee、Chandana Lakshmi T. Meda、Girdhar Singh Deora、K. Lalith Kumar、Ankit Jain、Girish H. Chaudhari、Keerthana S. Chennubhotla、Rakesh K. Banote、Pushkar Kulkarni、Kishore V. L. Parsa、K. Mukkanti、Manojit Pal

  DOI：10.1039/c3ob27424a

  日期：——

  A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

  描述了一种将抗精神病药物奥氮平转化为PDE4抑制剂的新策略，通过设计和Pd/C介导合成新型N-吲哚基甲基奥氮平衍生物。一种化合物表现出良好的抑制作用（IC50 1.1 μM），并且对PDE4B的选择性超过PDE4D超过10倍，这得到了对接研究的支持。该化合物还显示出显著抑制TNF-α，并且在细胞系和斑马鱼胚胎模型中没有明显的毒性，除了在啮齿动物中需要重新评估的致畸效应。
• 1,2,3-Triazoles derived from olanzapine: their synthesis via an ultrasound assisted CuAAC method and evaluation as inhibitors of PDE4B
  作者：Suresh Babu Nallapati、B. Yogi Sreenivas、Ramudu Bankala、Kishore V. L. Parsa、Shivashankar Sripelly、K. Mukkanti、Manojit Pal

  DOI：10.1039/c5ra20380e

  日期：——

  An ultrasound assisted CuAAC method afforded novel 1,2,3-triazoles derived from olanzapine as inhibitors of PDE4B.

  一种超声波辅助的CuAAC方法提供了从奥兰扎平衍生的新型1,2,3-三唑作为PDE4B的抑制剂。