1-acetyl-4-(bromoacetyl)piperazine | 330809-39-7

• 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: 1-acetyl-4-(bromoacetyl)piperazine
• 英文别名: 1-(4-acetyl-1-piperazinyl)-2-bromo-Ethanone；1-(4-acetylpiperazin-1-yl)-2-bromoethanone
• CAS: 330809-39-7
• 化学式: C₈H₁₃BrN₂O₂
• 分子量: 249.107
• InChiKey: WURSUKHWYZCOLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-碘-4-氨基吡唑并[3,4-d]嘧啶 、 1-acetyl-4-(bromoacetyl)piperazine 在 alkali carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-(2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Development of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes

  摘要：

  Malaria remains a major health concern for a large percentage of the world's population. While great strides have been made in reducing mortality due to malaria, new strategies and therapies are still needed. Therapies that are capable of blocking the transmission of Plasmodium parasites are particularly attractive, but only primaquine accomplishes this, and toxicity issues hamper its widespread use. In this study, we describe a series of pyrazolopyrimidine- and imidazopyrazine-based compounds that are potent inhibitors of PfCDPK4, which is a calcium-activated Plasmodium protein lcinase that is essential for exflagellation of male gametocytes. Thus, PfCDPK4 is essential for the sexual development of Plasmodium parasites and their ability to infect mosquitoes. We demonstrate that two structural features in the ATPbinding site of PfCDPK4 can be exploited in order to obtain potent and selective inhibitors of this enzyme. Furthermore, we demonstrate that pyrazolopyrimidine-based inhibitors that are potent inhibitors of the in vitro activity of PfCDPK4 are also able to block Plasmodium falciparum exflagellation with no observable toxicity to human cells. This medicinal chemistry effort serves as a valuable starting point in the development of safe, transmission-blocking agents for the control of malaria. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.048
• 作为产物：
  描述：

  1-乙酰哌嗪 、 溴乙酰溴 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到1-acetyl-4-(bromoacetyl)piperazine
  参考文献：
  名称：

  [DOTA-双（酰胺）]镧系元素络合物：NMR证据表明配位异构体的水分子交换速率不同。

  摘要：

  制备了带有反式乙酸酯和反式酰胺侧链连接基团的1,4,7,10-四氮杂十二烷的两种衍生物，并通过多核NMR光谱分析了它们与镧系元素阳离子的配合物。这些镧系元素络合物以缓慢互变的配位异构体的混合物形式存在，其化学位移为1H，与先前报道的四乙酸（[Ln（dota）]-）和四酰胺的主要（M）和次要（m）形式相似。 （[Ln（dtma）] 3+）复合物。与[Ln（dota）]-和[Ln（dtma）] 3+配合物一样，m / M比被证明是镧系元素大小和温度的敏感函数。对Yb3 +配合物的光谱进行1H超精细位移分析，发现m和M配位异构体的磁化率张量各向异性的轴向（D1）和非轴向（D2）分量之间存在显着差异，并且环反转和m的能级通过二维交换光谱法（EXSY）测定的M异构化。Dy3 +配合物的（17）O位移数据表明它们都具有一个内球水分子。Gd3 +配合物溶液的本体水线宽的温度依赖性（17）O NMR研究提

  DOI：

  10.1002/1521-3765(20010105)7:1<288::aid-chem288>3.0.co;2-6

文献信息

• Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues
  作者：Wenxi Wu、Yu Mu、Bo Liu、Zixuan Wang、Peipei Guan、Li Han、Mingguo Jiang、Xueshi Huang

  DOI：10.1016/j.bioorg.2021.104898

  日期：2021.6

  violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide

  Violacin A 是一种色满酮衍生物，从Streptomyces violaceoruber的发酵液中分离出来，具有出色的抗炎潜力。在此，描述了一种合成紫罗兰 A 和 25 种类似物的生物遗传学建模方法，该方法涉及通过克莱森缩合及其自发环化制备芳香聚酮化合物前体。通过脂多糖 (LPS) 诱导的 Raw264.7 细胞评估对所有合成分子的一氧化氮 (NO) 产生的抑制作用。结果表明，在C-7上引入脂肪胺基团明显提高了violacin A的抗炎作用，并且侧链上的芳香醚代替酮基有利于提高活性。其中，模拟7a和16d被筛选为最有效的抗炎候选药物。分子机制研究表明，7a和16d由于抑制NF-κB信号通路而获得抗炎能力。
• [EN] NEW 2, 1 L -DIAZA-[3.3](2,6)PYRIDINOPHANE COMPOUNDS AND THEIR APPLICATION AS LIGANDS OF ESSENTIAL METAL ION BASED MRI CONTRAST AGENTS AND 52MN BASED PET CONTRAST AGENTS<br/>[FR] NOUVEAUX COMPOSÉS 2, 1 L-DIAZA-[3,3](2,6)PYRIDINOPHANE ET LEUR APPLICATION COMME LIGANDS D'AGENTS DE CONTRASTE IRM À BASE DE D'IONS MÉTALLIQUES ESSENTIELS ET D'AGENTS DE CONTRASTE TEP À BASE DE 52MN
  申请人：DEBRECENI EGYETEM

  公开号：WO2017089848A1

  公开（公告）日：2017-06-01

  The one subject of the invention is the compounds of general formula (I), their isomers, their physiologically acceptable salts and/or Mn(II), Fe(II), Fe(III), Co(II) and Ni(II) complexes. The other subject of the invention is the application of the above compounds. The compounds of general formula (I): wherein -NRR1 group may refer to: a) -NRR1 with N atom in the ring means a ring of 4 to 7, that in certain cases may contain another heteroatom, and in specific cases the ring may be replaced with an aryl group (of 5 to 7 carbon atoms) substituted with -COOH, -OH, -OCH3, -NO2, -NH2, -NCS, -NHS- activated ester, aryl (of 5 to 7 carbon atoms), or nitro-, amino- or isothiocyanate group, or b) in the -NRR1 group R means a H atom, alkyl, aryl, nitroaryl, aminoaryl or isothiocyanate-aryl group (of 1 to 6 carbon atoms) and R4 is a H atom, alkyl (of 1 to 6 carbon atoms) or -(CH2)n-COOH group, whereas n=1 to 10 integer, or c) -NRR1 group is one of the following groups: (formula II) whereas R2 is a H atom, carboxyl- or alkyl-carbonyl group (of 1 to 4 carbon atoms);(formula III) and R2 is a H atom or alkyl or aryl group (of 1 to 6 carbon atoms), and X means independently from one another H atom, -CH3, -COOH, -OH, -OCH3, alkoxy- (of 2 to 6 carbon atoms), -NO2, -NH2, -NCS, -NHS -activated ester, alkyl (of 2 to 12 carbon atoms) or aryl (of 5 to 7 carbon atoms) group, in certain cases the latter may be substituted with hydroxyl, hydroxyalkyl (of 1 to 6 carbon atoms), nitro, amino or isothiocyanate group.

  本发明的一个主题是通式（I）的化合物，它们的异构体，其生理上可接受的盐和/或Mn（II），Fe（II），Fe（III），Co（II）和Ni（II）配合物。本发明的另一个主题是上述化合物的应用。通式（I）的化合物：其中-NRR1基团可能指：a）-NRR1中带有环中的N原子意味着一个由4至7个环组成的环，在某些情况下可能含有另一个杂原子，并且在特定情况下该环可能被取代为一个芳基（由5至7个碳原子）取代为-COOH，-OH，-O ，-NO2，-NH2，-NCS，-NHS-活化酯，芳基（由5至7个碳原子），或硝基，氨基或异硫氰酸酯基团，或b）在-NRR1基团中R表示H原子，烷基，芳基，硝基芳基，氨基芳基或异硫氰酸酯芳基（由1至6个碳原子）和R4是H原子，烷基（由1至6个碳原子）或-(CH2)n-COOH基团，其中n=1至10的整数，或c）-NRR1基团是以下基团之一：（式II）其中R2是H原子，羧基或烷基羰基基团（由1至4个碳原子）；（式III）且R2是H原子或烷基或芳基（由1至6个碳原子）基团，X分别独立于H原子，-CH3，-COOH，-OH，-O ，烷氧基（由2至6个碳原子），- ，-NH2，-NCS，-NHS-活化酯，烷基（由2至12个碳原子）或芳基（由5至7个碳原子）基团，在某些情况下后者可能被取代为羟基，羟基烷基（由1至6个碳原子），硝基，氨基或异硫氰酸酯基团。
• [EN] NEW 6-OXA-3,9, 15-TRIAZA-BICYCLO[9.3.1 ]PENTADEC A- 1 ( 14), 1 1 ( 15), 12-TRIENE DERIVATIVES BASED COMPOUNDS AND THEIR APPLICATION AS LIGANDS OF ESSENTIAL METAL ION BASED MRI AND 52MN BASED PET CONTRAST AGENTS<br/>[FR] NOUVEAUX COMPOSÉS À BASE DE DÉRIVÉS DE 6-OXA-3,9,15-TRIAZA-BICYCLO[9.3.1]PENTADÉCA-1(14),11(15),12-TRIENE ET LEUR APPLICATION À TITRE DE LIGANDS D'AGENTS DE CONTRASTE IRM ESSENTIELS À BASE D'IONS MÉTALLIQUES ET D'AGENTS DE CONTRASTE PET ESSENTIELS À BASE DE 52MN
  申请人：DEBRECENI EGYETEM

  公开号：WO2017089849A1

  公开（公告）日：2017-06-01

  The one subject of the invention is the compounds of general formula (I), their isomers, their physiologically acceptable salts and/or Mn(ll), Fe(ll), Fe(lll), Co(ll) and Ni(ll) complexes and their application: where R1| = - OH or -NR 3 R 4 amide functionality

  本发明的一个主题是一般式(I)的化合物，它们的异构体，它们的生理上可接受的盐和/或Mn(ll)、Fe(ll)、Fe(lll)、Co(ll)和Ni(ll)配合物及其应用：其中R1| = - OH或-NR 3 R 4 酰胺官能团
• [EN] NEW 3,6,9, 15-TETRAAZA-BICYCLO [9.3.1 ]PENTADECA- 1(14), 11(15), 12-TRIENE BASED COMPOUNDS AND THEIR APPLICATION AS LIGANDS OF ESSENTIAL METAL ION BASED MRI AND 52MN BASED PET CONTRAST AGENTS<br/>[FR] NOUVEAUX COMPOSÉS À BASE DE 3,6,9,15-TÉTRAAZA-BICYCLO [9.3.1]PENTADÉCA-1(14),11(15),12-TRIÈNE ET LEUR APPLICATION COMME LIGANDS D'AGENTS DE CONTRASTE POUR IRM À BASE D'IONS MÉTALLIQUES ET POUR TEP À BASE DE 52MN
  申请人：DEBRECENI EGYETEM

  公开号：WO2017089847A1

  公开（公告）日：2017-06-01

  The one subject of the invention is the compounds of general formula (I), their isomers, their physiologically acceptable salts and/or Mn(II), Fe(II), Fe(III), Co(II) and Ni(II) complexes. The other subject of the invention is the application of the above compounds. The compounds of general formula (I): wherein Ra refers to -OH group or -NR3R4 group and -NR3R4 group may refer to: a) -NR3R4 with N atom in the ring means a ring of 4 to 7, that in certain cases may contain another heteroatom, and in specific cases the ring may be replaced with an aryl group (of 5 to 7 carbon atoms) substituted with -COOH, -OH, -OCH3, -NO2, -NH2, -NCS, -NHS- activated ester, aryl (of 5 to 7 carbon atoms), or nitro-, amino- or isothiocyanate group, or b) in the -NR3R4 group R3 means a H atom, alkyl, aryl, nitroaryl, aminoaryl or isothiocyanate-aryl group (of 1 to 6 carbon atoms) and R4 is a H atom, alkyl (of 1 to 6 carbon atoms) or -(CH2)n-COOH group, whereas n=1 to 10 integer, or c) -NR3R4 group is one of the below groups: whereas R1 is a H atom, carboxyl or alkyl-carbonyl group (of 1 to 4 carbon atoms); and Rb is a H atom or alkyl group (of 1 to 6 carbon atoms), and X means independently from one another H atom, -CH3, -COOH, -OH, -OCH3, alkoxy- (of 2 to 6 carbon atoms), -NO2, -NH2, -NCS, -NHS-activated ester, alkyl (of 2 to 12 carbon atoms) or aryl (of 5 to 7 carbon atoms) group, in certain cases the latter may be substituted with hydroxyl, hydroxyalkyl (of 1 to 6 carbon atoms), nitro, amino or isothiocyanate group; and Y means: -NH- or >NCH2-Z group, whereas in the >CH2-Z group Z refers to one selected group of the below: -C(O)NR3R4 group, in which -NR3R4 means as referred to above, whereas z= 0- 18 integer, whereas z=0-18 integer, whereas z=0-18 integer, whereas z=0-18 integer and H atom, alkyl (of 1 to 6 carbon atoms) or -(CH2)n-COOH group, whereas n=l to 10 integer, or, whereas z= 0-18 integer, whereas z=0-18 integer and R2a refers to H atom, -OCH3, or -CF3 group, whereas R2b refers to H atom, -CH3, -OCH3>.CF3; - COOH, -COON(CO)2(CH2)2, -NO2, -NH2 or -NCS- group, whereas z= 0-18 integer and R2c refers to H atom, NO2, -NH2 or -NCS- group, whereas ζ=0-18, -and x=l-5 integer, whereas z=0-18,, and x=1.5 integer; whereas z=1-5, and x=1-5 integer, R2d refers to H atom, -CH3, -OCH3;.CF3, -COOH, - COON(CO)2(CH2)2, -NO2, -NH2 or -NCS group,

  本发明的一个主题是通式（I）的化合物，它们的异构体，它们的生理可接受的盐和/或Mn（II），Fe（II），Fe（III），Co（II）和Ni（II）络合物。该发明的另一个主题是上述化合物的应用。通式（I）的化合物：其中Ra代表-OH基团或-NR3R4基团，而-NR3R4基团可能指：a）-NR3R4，环中的N原子表示4至7的环，在某些情况下可能含有另一个杂原子，并且在特定情况下环可能被取代为芳基（5至7个碳原子）取代为-COOH，-OH，-O ，-NO2，-NH2，-NCS，-NHS-活化酯，芳基（5至7个碳原子），或硝基，氨基或异硫氰酸酯基团，或b）在-NR3R4基团中，R3表示H原子，烷基，芳基，硝基芳基，氨基芳基或异硫氰酸酯芳基（1至6个碳原子），而R4是H原子，烷基（1至6个碳原子）或-(CH2)n-COOH基团，其中n=1至10整数，或c）-NR3R4基团是以下基团之一：其中R1是H原子，羧基或烷基羰基基团（1至4个碳原子）；而Rb是H原子或烷基基团（1至6个碳原子），X分别独立于H原子，-CH3，-COOH，-OH，-O ，烷氧基（2至6个碳原子），- ，-NH2，-NCS，-NHS-活化酯，烷基（2至12个碳原子）或芳基（5至7个碳原子）基团，在某些情况下后者可能被羟基，羟基烷基（1至6个碳原子），硝基，氨基或异硫氰酸酯基团取代；而Y表示：-NH-或>N -Z基团，其中在>N -Z基团中，Z指下列选定的基团之一：-C（O）NR3R4基团，其中-NR3R4如上所述，其中z=0-18整数，其中z=0-18整数，其中z=0-18整数，其中z=0-18整数和H原子，烷基（1至6个碳原子）或-( )n-COOH基团，其中n=1至10整数，或，其中z=0-18整数，其中z=0-18整数，其中R2a指H原子，-O ，或-CF3基团，而R2b指H原子，- ，-O >. ；-COOH，-COON（CO）2（ ）2，- ，-NH2或-NCS-基团，其中z=0-18整数，而R2c指H原子， ，-NH2或-NCS-基团，而ζ=0-18，-和x=1-5整数，其中z=0-18，，和x=1.5整数；其中z=1-5，，和x=1-5整数，R2d指H原子，- ，-O ；. ，-COOH，-COON（CO）2（ ）2，- ，-NH2或-NCS基团。
• Use of oxindole derivatives in the treatment of dementia related diseases, alzheimer's disease and conditions associated with glycogen synthase kinase-3
  申请人：Berg Stefan

  公开号：US20050070559A1

  公开（公告）日：2005-03-31

  The present invention relates to a new use of oxindole derivatives of formula I, as a free base or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , m and n arm as defined as in claim 1, as well as to new compounds, a process for their preparation and new intermediates used in the preparation thereof, pharmaceutical compositions containing said therapeutically active compounds and to the use of said active compounds in therapy, especially in the prevention and/or treatment of dementia related diseases, Alzheimer's Disease and conditions associated with glycogen synthase kinase-3.

  本发明涉及一种公式I的氧化吲哚衍生物的新用途，作为其自由碱基或药学上可接受的盐，其中R1、R2、R3、m和n的定义如权利要求书1所述。同时涉及新化合物、其制备方法以及用于制备新化合物的新中间体，含有所述治疗活性化合物的药物组合物以及所述活性化合物在治疗中的应用，特别是在预防和/或治疗与糖原合成酶激酶-3相关的痴呆症、阿尔茨海默病和条件方面的应用。