4-((methyl(1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-yl)amino)methyl)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((methyl(1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-yl)amino)methyl)benzonitrile
• 英文别名: N-methyl-N-(4-cyanobenzyl)-N-[1-(2-methylthiopyrimidin-4-yl)piperidin-4-yl]amine；N-(4-cyanobenzyl)-N-methyl-1-(2-methylthiopyrimidin-4-yl) piperidin-4-amine；HSP70-36；N-(4-Cyanobenzyl)-N-methyl-1-(2-methylthiopyrimidin-4-yl)piperidin-4-amine；4-[[methyl-[1-(2-methylsulfanylpyrimidin-4-yl)piperidin-4-yl]amino]methyl]benzonitrile
• 化学式: C₁₉H₂₃N₅S
• 分子量: 353.491
• InChiKey: BNIWFONQLUMHJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((methyl(1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-yl)amino)methyl)benzonitrile 在 盐酸 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 以160 mg的产率得到N-methyl-N-(4-cyanobenzyl)-N-[1-(2-methylthiopyrimidin-4-yl)piperidin-4-yl]amine hydrochloride
  参考文献：
  名称：

  N, N' SUBSTITUTED PIPERIDINAMINE COMPOUNDS, AND PREPARATION METHOD AND USAGE THEREOF

  摘要：

  公开号：

  EP3085701B1
• 作为产物：
  描述：

  1-叔丁氧羰基-4-甲氨基哌啶 在 盐酸 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 4-((methyl(1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-yl)amino)methyl)benzonitrile
  参考文献：
  名称：

  N,N-二烷基-1-(2-烷基硫代嘧啶-4-基)哌啶-4-胺作为潜在热休克蛋白抑制剂的合成

  摘要：

  一种合成有前景的热休克蛋白抑制剂 N,N-二烷基-1-(2-烷基硫代嘧啶-4-基)哌啶-4-胺的新方法，通过 2-烷基-4-氯硫尿嘧啶与 4-(开发了 N-烷基-N-甲基氨基）哌啶。2-烷基-4-氯硫氧嘧啶是通过用烷基碘对2-硫尿嘧啶进行烷基化反应，然后用POCl3 处理中间体来合成的。4-(N-烷基-N-甲基氨基)哌啶通过用甲胺还原胺化1-(叔丁氧基羰基)-4-哌啶酮然后用合适的醛处理中间体来制备。

  DOI：

  10.1007/s11172-018-2339-5

文献信息

• N,N′ substituted piperidinamine compounds, and preparation method and usage thereof
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：US10023565B2

  公开（公告）日：2018-07-17

  The present invention relates to a compound of formula (I), a stereomeride, pharmaceutically acceptable salt, a solvate or an N-oxide thereof, a medicine composition comprising the compound, a method for preparing the compound, and a usage of the compound in treating diseases related to Hsp70. The diseases are preferably selected from tumors, neurodegenerative diseases, and allogeneic transplantation rejection and infection.

  本发明涉及一种式(I)化合物、其立体异构体、药学上可接受的盐、溶液剂或N-氧化物，一种包含该化合物的药物组合物，一种制备该化合物的方法，以及该化合物在治疗与Hsp70有关的疾病中的用途。这些疾病优选选自肿瘤、神经退行性疾病、异体移植排斥和感染。
• [EN] N, N' SUBSTITUTED PIPERIDINAMINE COMPOUNDS, AND PREPARATION METHOD AND USAGE THEREOF<br/>[FR] COMPOSÉS N,N'-SUBSTITUÉS DE PIPÉRIDINAMINE, LEURS PROCÉDÉS DE PRÉPARATION ET UTILISATION CORRESPONDANTE<br/>[ZH] N，N'取代哌啶胺类化合物、其制备方法及用途
  申请人：INST PHARM & TOXICOLOGY AMMS

  公开号：WO2015090226A1

  公开（公告）日：2015-06-25

  本发明涉及式（I）的化合物、其立体异构体、可药用盐、溶剂化物或N-氧化物，包含所述化合物的药物组合物，所述化合物的制备方法，以及所述化合物用于治疗与Hsp70有关的疾病中的用途，其中所述疾病优选选自肿瘤、神经退行性疾病、异源移植的排斥和感染。
• Design and synthesis of piperidine derivatives as novel human heat shock protein 70 inhibitors for the treatment of drug-resistant tumors
  作者：Yanqun Zeng、Ruiyuan Cao、Tianhong Zhang、Song Li、Wu Zhong

  DOI：10.1016/j.ejmech.2015.04.043

  日期：2015.6

  HSP70 is a potential target for tumour treatment. HSP70 plays significant roles in several biological processes, including the regulation of apoptosis. In this study, piperidine derivatives were designed as novel HSP70 inhibitors based on virtual fragment screening performed in Dock 4.0, Discovery Studio 2.5 and SYBYL 6.9. A total of 67 novel piperidine derivatives were synthesized. Cell viability assays were performed in 16 cancer cell lines. The emphasis was placed on lapatinib-resistant breast cancer cells (BT/LapR1.0, MDA-MB-361, SK/Lap(R)1.0, and MDA-MB-453). The compounds HSP70-36/37/40/43146 significantly inhibited the proliferation of human breast cancer cells. Compound HSP70-36 inhibited the growth of BT474 and BT/Lap(R)1.0 cells with IC50 values of 1.41 mu M and 1.47 mu M, respectively. The binding affinity of HSP70-36/HSP70 was evaluated by surface plasmon resonance and yielded K-d values of 2.46 mu M. The LD50 was 869.0 mgkg(-1). These data suggest that HSP70-36 may be a potential candidate compound for tumour treatment. (C) 2015 The Authors. Published by Elsevier Masson SAS.
• Synthesis of N,N-dialkyl-1-(2-alkylthiopyrimidin-4-yl)piperidin- 4-amines as potential heat shock protein inhibitors
  作者：V. N. Aldobaev、M. A. Prezent、I. V. Zavarzin

  DOI：10.1007/s11172-018-2339-5

  日期：2018.11

  A new efficient method for synthesizing promising heat shock protein inhibitors, N,N-dialkyl- 1-(2-alkylthiopyrimidin-4-yl)piperidin-4-amines, by the reaction of 2-alkyl-4-chlorothiouracils with 4-(N-alkyl-N-methylamino)piperidines was developed. 2-Alkyl-4-chlorothiouracils were synthesized by alkylation of 2-thiouracil with alkyl iodides and subsequent treatment of the intermediates with POCl3. 4

  一种合成有前景的热休克蛋白抑制剂 N,N-二烷基-1-(2-烷基硫代嘧啶-4-基)哌啶-4-胺的新方法，通过 2-烷基-4-氯硫尿嘧啶与 4-(开发了 N-烷基-N-甲基氨基）哌啶。2-烷基-4-氯硫氧嘧啶是通过用烷基碘对2-硫尿嘧啶进行烷基化反应，然后用POCl3 处理中间体来合成的。4-(N-烷基-N-甲基氨基)哌啶通过用甲胺还原胺化1-(叔丁氧基羰基)-4-哌啶酮然后用合适的醛处理中间体来制备。
• N, N' SUBSTITUTED PIPERIDINAMINE COMPOUNDS, AND PREPARATION METHOD AND USAGE THEREOF
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：EP3085701B1

  公开（公告）日：2019-02-20