4-甲基哌嗪-1-甲脒半硫酸盐 | 28457-20-7

• 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: 4-甲基哌嗪-1-甲脒半硫酸盐
• 中文别名: 4-甲基哌嗪-1-羧胺半硫酸盐
• 英文名称: 1-methyl-4-piperazinecarboxamidine hydrogen sulfate
• 英文别名: 4-methylpiperazine-1-carboxamidinium sulfate；4-methyl-piperazine-1-carboxamidine sulfate；4-Methylpiperazine-1-carboximidamide sulfate；4-methylpiperazine-1-carboximidamide;sulfuric acid
• CAS: 28457-20-7
• 化学式: C₆H₁₄N₄*H₂O₄S
• 分子量: 240.283
• InChiKey: OWFBETMVTYKOTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.53
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-甲基哌嗪-1-甲脒半硫酸盐 在 sodium methylate 、 三氯氧磷 作用下， 反应 8.5h， 生成 4,5,6-Trichloro-2-(4-methyl-piperazin-1-yl)-pyrimidine
  参考文献：
  名称：

  4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for .alpha.2-adrenoceptors

  摘要：

  A series of 4-amino-6-chloro-2-piperazinopyrimidines were synthesized and evaluated for their ability to interact with alpha 1- and alpha 2-adrenoceptors in vitro in binding assays using [3H]WB-4101, [3H]clonidine, and [3H]idazoxan as radioligands. Some compounds were also tested as inhibitors of [3H]spiroperidol binding. Several members of this series showed high and selective affinity for alpha 2-adrenoceptors. The nature of the 4-amino substituent seems to be the most critical factor in determining the potency at these receptors.

  DOI：

  10.1021/jm00158a013
• 作为产物：
  描述：

  S-甲基异硫脲硫酸盐 、 N-甲基哌嗪 以 水 为溶剂， 反应 0.25h， 生成 4-甲基哌嗪-1-甲脒半硫酸盐
  参考文献：
  名称：

  抗疟疾活性和新的三取代嘧啶的合成。

  摘要：

  合成了一系列的2,4,6-三取代-嘧啶并评估了它们对恶性疟原虫的体外抗疟活性。在合成的30种化合物中，有21种化合物的MIC在0.5-2 microg / mL范围内。这些化合物在体外的活性是乙胺嘧啶的几倍。

  DOI：

  10.1016/j.bmcl.2005.04.014

文献信息

• Saturated heterocycles.<b>242</b>. Synthesis of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydro- quinazolin-4(3<i>H</i>)-one Derivatives
  作者：Gábor Bernáth、János Lázár、Ferenc Fülöp、Jenó Kóbor

  DOI：10.1002/jhet.5570330668

  日期：1996.11

  synthesized β-ketoesters 1-[(3′-methoxycarbonyl- and 1-[(3′-ethoxycarbonyl-4′-oxo)-1′-cyclohexyl]-3,4-dihydroisoquinoline 4, 5 with amidines or cyclic guanidines, a number of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one derivatives 6–8 were prepared. The new compounds possess various pharmacological actions.

  在最近合成的β-酮酸酯1-[（（3'-甲氧羰基-和1-[（3'-乙氧羰基-4'-氧代）-1'-环己基] -3,4-二氢异喹啉] 4，5与or或环状胍，一些2-取代的-6-（6'，7'-二甲氧基-3'，4'-二氢-1'-异喹啉基）-5,6,7,8-四氢喹唑啉-4（3制备了H）-一衍生物6-8，该新化合物具有多种药理作用。
• Substituted nitrogen-containing heteroaryl derivatives useful as modulators of the histamine H4 receptor
  申请人：Gaul Michael D.

  公开号：US20090069305A1

  公开（公告）日：2009-03-12

  The present invention relates to substituted nitrogen-containing heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using any of these derivatives and compositions for H 4 receptor activity modulation and the treatment of states mediated by histamine H 4 receptor activity.

  本发明涉及取代的含氮杂芳基衍生物、含有它们的药物组合物，以及使用这些衍生物和组合物中的任一种用于调节H4受体活性和治疗由组胺H4受体活性介导的状态的方法。
• Inhibition of the SR Protein-Phosphorylating CLK Kinases of Plasmodium falciparum Impairs Blood Stage Replication and Malaria Transmission
  作者：Selina Kern、Shruti Agarwal、Kilian Huber、André P. Gehring、Benjamin Strödke、Christine C. Wirth、Thomas Brügl、Liliane Onambele Abodo、Thomas Dandekar、Christian Doerig、Rainer Fischer、Andrew B. Tobin、Mahmood M. Alam、Franz Bracher、Gabriele Pradel

  DOI：10.1371/journal.pone.0105732

  日期：——

  Cyclin-dependent kinase-like kinases (CLKs) are dual specificity protein kinases that phosphorylate Serine/Arginine-rich (SR) proteins involved in pre-mRNA processing. Four CLKs, termed PfCLK-1-4, can be identified in the human malaria parasite Plasmodium falciparum, which show homology with the yeast SR protein kinase Sky1p. The four PfCLKs are present in the nucleus and cytoplasm of the asexual blood stages and of gametocytes, sexual precursor cells crucial for malaria parasite transmission from humans to mosquitoes. We identified three plasmodial SR proteins, PfSRSF12, PfSFRS4 and PfSF-1, which are predominantly present in the nucleus of blood stage trophozoites, PfSRSF12 and PfSF-1 are further detectable in the nucleus of gametocytes. We found that recombinantly expressed SR proteins comprising the Arginine/Serine (RS)-rich domains were phosphorylated by the four PfCLKs in in vitro kinase assays, while a recombinant PfSF-1 peptide lacking the RS-rich domain was not phosphorylated. Since it was hitherto not possible to knock-out the pfclk genes by conventional gene disruption, we aimed at chemical knock-outs for phenotype analysis. We identified five human CLK inhibitors, belonging to the oxo-β-carbolines and aminopyrimidines, as well as the antiseptic chlorhexidine as PfCLK-targeting compounds. The six inhibitors block P. falciparum blood stage replication in the low micromolar to nanomolar range by preventing the trophozoite-to-schizont transformation. In addition, the inhibitors impair gametocyte maturation and gametogenesis in in vitro assays. The combined data show that the four PfCLKs are involved in phosphorylation of SR proteins with essential functions for the blood and sexual stages of the malaria parasite, thus pointing to the kinases as promising targets for antimalarial and transmission blocking drugs.

  细胞周期蛋白依赖性激酶样激酶（CLKs）是一种双重特异性蛋白激酶，可使参与前核糖核酸（mRNA）加工的富丝氨酸/精氨酸（SR）蛋白磷酸化。在人类疟原虫恶性疟原虫中发现了四种 CLK，称为 PfCLK-1-4，它们与酵母 SR 蛋白激酶 Sky1p 同源。这四种 PfCLK 存在于无性血液阶段和配子细胞的细胞核和细胞质中，配子细胞是疟原虫从人类向蚊子传播的关键有性前体细胞。我们发现了三种质体 SR 蛋白，即 PfSRSF12、PfSFRS4 和 PfSF-1，它们主要存在于血期滋养体的细胞核中，PfSRSF12 和 PfSF-1 还可在配子细胞的细胞核中检测到。我们发现，在体外激酶试验中，重组表达的富含精氨酸/丝氨酸（RS）结构域的 SR 蛋白会被四种 PfCLK 磷酸化，而缺乏富含 RS 结构域的重组 PfSF-1 肽则不会被磷酸化。由于迄今为止还无法通过传统的基因敲除方法敲除 pfclk 基因，我们的目标是通过化学方法敲除 pfclk 基因以进行表型分析。我们确定了五种人类 CLK 抑制剂（属于氧化-β-咔啉类和氨基嘧啶类）以及杀菌剂洗必泰作为 PfCLK 靶向化合物。这六种抑制剂通过阻止滋养体向裂殖体的转化，在微摩尔至纳摩尔的低浓度范围内阻断恶性疟原虫血液阶段的复制。此外，在体外试验中，这些抑制剂还会损害配子细胞的成熟和配子的产生。综合数据表明，这四种 PfCLK 参与了 SR 蛋白的磷酸化过程，而 SR 蛋白对疟原虫的血液阶段和有性阶段具有重要功能，因此这些激酶有望成为抗疟药物和传播阻断药物的靶点。
• Antimalarial activity and synthesis of new trisubstituted pyrimidines
  作者：Anu Agarwal、Kumkum Srivastava、S.K. Puri、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2005.04.014

  日期：2005.6

  A series of 2,4,6-trisubstituted-pyrimidines was synthesized and evaluated for their in vitro antimalarial activity against Plasmodium falciparum. Out of the 30 compounds synthesized 21 compounds showed MIC in the range of 0.5-2 microg/mL. These compounds are in vitro several folds more active than pyrimethamine.

  合成了一系列的2,4,6-三取代-嘧啶并评估了它们对恶性疟原虫的体外抗疟活性。在合成的30种化合物中，有21种化合物的MIC在0.5-2 microg / mL范围内。这些化合物在体外的活性是乙胺嘧啶的几倍。
• Efficient Copper-Catalyzed Synthesis of 2-Amino-4(<i>3H</i>)-quinazolinone and 2-Aminoquinazoline Derivatives
  作者：Hua Fu、Renzhong Qiao、Xuhu Huang、Haijun Yang、Yufen Zhao

  DOI：10.1055/s-0029-1216871

  日期：——

  We have developed a versatile and efficient method for copper-catalyzed synthesis of both 2-amino-4(3H)-quinazolinone and 2-aminoquinazoline derivatives. The protocol uses readily available substituted 2-halobenzoic acids, 2-bromobenzaldehyde, 2-bromophenyl ketones and guanidines as the starting materials, inexpensive copper(I) iodide as the catalyst, and the method has important application values

  我们已经开发了一种通用且有效的方法，用于铜催化的2-氨基-4（3H）-喹唑啉酮和2-氨基喹唑啉衍生物的合成。该方案使用容易获得的取代的2-卤代苯甲酸，2-溴苯甲醛，2-溴苯基酮和胍作为起始原料，廉价的碘化亚铜（I）作为催化剂，该方法对于在N-杂环结构中的应用具有重要的应用价值。有机化学和药物化学。 铜催化-交叉偶联-2-氨基-4（3H）-喹唑啉酮-2-氨基喹唑啉-合成方法