1-(3-丁炔-1-基)-4-甲基哌嗪 | 388121-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(3-丁炔-1-基)-4-甲基哌嗪
• 英文名称: 1-(3-butynyl)-4-methyl-piperazine
• 英文别名: 1-but-3-ynyl-4-methylpiperazine
• CAS: 388121-83-3
• 化学式: C₉H₁₆N₂
• 分子量: 152.239
• InChiKey: GZBWIJDICIGGKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-丁炔-1-基)-4-甲基哌嗪 在 吡啶 、 正丁基锂 、 吡啶盐酸盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 5-(4-Methyl-piperazin-1-yl)-pent-2-ynoic acid [4-(3-bromo-4-fluoro-phenylamino)-pyrido[3,4-d]pyrimidin-6-yl]-amide
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 19. 6-Alkynamides of 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Irreversible Inhibitors of the erbB Family of Tyrosine Kinase Receptors

  摘要：

  Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of alkynamide analogues of quinazoline- and pyrido[3,4-d]pyrimidine-based compounds. The compounds were prepared by coupling the appropriate 6-aminoquinazolines or 6-aminopyrido[3,4-d]pyrimidines with alkynoic acids, using EDCI center dot HCl in pyridine. The compounds showed pan-erbB enzyme inhibition but were on average about 10-fold more potent against erbB1 than against erbB2 and erbB4. For cellular inhibition, the nature of the alkylating side chains was an important determinant, with 5-dialkylamino-2-pentynamide type Michael acceptors providing the highest potency. This is suggested to be due to an improved ability of the amine to participate in an autocatalysis of the Michael reaction with enzyme cysteine residues. Pyrido[3,4-d]pyrimidine analogue 39 was selected for in vivo evaluation and achieved tumor regressions at 10 mg/kg in the A431 human epidermoid carcinoma and at 40 mg/kg for the SF767 human glioblastoma and the SKOV3 human ovarian carcinoma. Complete stasis was observed at 40 mg/kg in the BXPC3 human pancreatic carcinoma as well as in the H125 human non-small-cell lung carcinoma.

  DOI：

  10.1021/jm050936o
• 作为产物：
  描述：

  N-甲基哌嗪 、 对甲苯磺酸 3-丁炔酯 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以12%的产率得到1-(3-丁炔-1-基)-4-甲基哌嗪
  参考文献：
  名称：

  基于二胺的人组胺H 3受体拮抗剂：（4-氨基丁炔-1-基）苄胺

  摘要：

  制备了一系列（4-氨基丁炔-1-基）苄胺，SAR围绕三个关键区域：（1）与丁炔基连接基（R 3 R 4 N–）相连的胺；（2）苄胺部分（R 1 R 2 N–）；（3）检查了苄胺基团的连接点（R 1 R 2 N–在邻位，间位或对位）。选择一种化合物4- [3-（4-哌啶-1-基-丁-1-炔基）-苄基]-吗啉（9s）进行进一步分析，结果发现它是一种选择性的组胺H 3拮抗剂，具有所需的药物-像属性。离体受体占用研究确定口服后9s确实在大鼠的大脑中占据了H 3结合位点。在自然睡眠阶段皮下注射的9s（10 mg / kg）表现出强大的促醒作用。

  DOI：

  10.1016/j.ejmech.2009.04.049

文献信息

• Pyrroloquinolones as antiviral agents
  申请人：——

  公开号：US20020055636A1

  公开（公告）日：2002-05-09

  The present invention provides a compound of formula I 1 which is useful as antiviral agents, in particular, as agents against viruses of the herpes family.

  本发明提供了一种化合物，其化学式为I，可用作抗病毒剂，特别是用于抗击疱疹病毒家族的药剂。
• Triarylpyridine Compounds and Chloroquine Act in Concert to Trigger Lysosomal Membrane Permeabilization and Cell Death in Cancer Cells
  作者：Jennifer Beauvarlet、Rabindra Nath Das、Karla Alvarez-Valadez、Isabelle Martins、Alexandra Muller、Elodie Darbo、Elodie Richard、Pierre Soubeyran、Guido Kroemer、Jean Guillon、Jean-Louis Mergny、Mojgan Djavaheri-Mergny

  DOI：10.3390/cancers12061621

  日期：——

  Lysosomes play a key role in regulating cell death in response to cancer therapies, yet little is known on the possible role of lysosomes in the therapeutic efficacy of G-quadruplex DNA ligands (G4L) in cancer cells. Here, we investigate the relationship between the modulation of lysosomal membrane damage and the degree to which cancer cells respond to the cytotoxic effects of G-quadruplex ligands belonging to the triarylpyridine family. Our results reveal that the lead compound of this family, 20A promotes the enlargement of the lysosome compartment as well as the induction of lysosome-relevant mRNAs. Interestingly, the combination of 20A and chloroquine (an inhibitor of lysosomal functions) led to a significant induction of lysosomal membrane permeabilization coupled to massive cell death. Similar effects were observed when chloroquine was added to three new triarylpyridine derivatives. Our findings thus uncover the lysosomal effects of triarylpyridines compounds and delineate a rationale for combining these compounds with chloroquine to increase their anticancer effects.

  溶酶体在调节细胞对癌症治疗的死亡起着关键作用，然而对溶酶体在G-四链体DNA连接物（G4L）对癌细胞的治疗效果中可能发挥的作用知之甚少。在这里，我们研究了溶酶体膜损伤的调节与癌细胞对属于三芳基吡啶家族的G-四链体配体的细胞毒效应之间的关系。我们的结果显示，该家族的主要化合物20A促进了溶酶体区的扩大以及溶酶体相关mRNA的诱导。有趣的是，20A与氯喹（一种溶酶体功能抑制剂）的组合导致了溶酶体膜通透性的显著诱导，伴随着大规模的细胞死亡。当氯喹添加到三种新的三芳基吡啶衍生物中时，也观察到了类似的效应。因此，我们的发现揭示了三芳基吡啶化合物的溶酶体效应，并勾勒出了将这些化合物与氯喹结合以增强其抗癌效果的合理性。
• ALKYNYL PYRROLOPYRIMIDINES AND RELATED ANALOGS AS HSP90-INHIBITORS
  申请人：Kasibhatla Rao Srinivas

  公开号：US20060223797A1

  公开（公告）日：2006-10-05

  Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

  炔基吡咯并[2,3-d]嘧啶及相关类似物被描述并证明具有作为热休克蛋白90（HSP90）抑制剂的效用，用于治疗和预防各种HSP90介导的疾病。还描述和声明了这类化合物的合成和使用方法。
• Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities
  作者：Bernhard Stump、Christian Eberle、Marcel Kaiser、Reto Brun、R. Luise Krauth-Siegel、François Diederich

  DOI：10.1039/b806371k

  日期：——

  Trypanothione reductase (TR) is an essential enzyme of trypanosomatids and therefore a promising target for the development of new drugs against African sleeping sickness and Chagas' disease. Diaryl sulfides with a central anilino moiety, decorated with a flexible N-alkyl side chain bearing a terminal ammonium ion, are a known class of inhibitors. Using computer modelling, we revised the binding model

  锥虫硫磷还原酶（TR）是锥虫的必不可少的酶，因此是开发抗非洲昏睡病和南美锥虫病新药的有希望的目标。具有中心苯胺基部分并用带有末端铵离子的柔性N-烷基侧链修饰的二芳基硫化物是已知的抑制剂。使用计算机建模，我们修改了这类TR抑制剂的结合模型，预测铵离子封端的N-烷基链与同二聚体第二个亚基的Glu18以及Glu465'/ Glu466'同时相互作用，而疏水取代基苯胺环的一部分在Trp21和Met113附近占据“ mepacrine结合位点”。抑制剂支架的羧酸盐结合片段和二芳基硫醚核的系统性改变为提出的结合模式提供了证据。体外研究表明，对布鲁氏锥虫和疟原虫恶性疟原虫的微摩尔至亚微摩尔范围内的低IC（50）值。
• Quinazoline derivatives
  申请人：——

  公开号：US20040116422A1

  公开（公告）日：2004-06-17

  A compound of the formula (I) 1 or a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, an optically active compound thereof, a racemate thereof or a diastereomer mixture thereof has a superior tyrosine-specific protein kinase inhibitory activity and is useful as a pharmaceutical agent, particularly as an agent for the prophylaxis or treatment of various cancers, psoriasis or diseases caused by arteriosclerosis, and the like.

  式（I）的化合物或其药学上可接受的盐、水合物、溶剂合物、光学活性化合物、消旋体或其二对映异构体混合物具有优越的酪氨酸特异性蛋白激酶抑制活性，并且可用作药物剂，特别是作为各种癌症、银屑病或由动脉硬化引起的疾病的预防或治疗剂。