7-n-butyl-6-(4-chlorophenyl)[5H]pyrrolo[2,3-b]-pyrazine | 496864-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 7-n-butyl-6-(4-chlorophenyl)[5H]pyrrolo[2,3-b]-pyrazine
• 英文别名: 7-n-butyl-6-(4-chlorophenyl)[5H]pyrrolo[2,3-b]pyrazine；7-butyl-6-(4-chlorophenyl)-5H-pyrrolo[2,3-b]pyrazine
• CAS: 496864-17-6
• 化学式: C₁₆H₁₆ClN₃
• 分子量: 285.776
• InChiKey: GKGBCENYMVXALT-UHFFFAOYSA-N

物化性质

• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对氯苯甲腈 、 正戊基吡嗪 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以70%的产率得到7-n-butyl-6-(4-chlorophenyl)[5H]pyrrolo[2,3-b]-pyrazine
  参考文献：
  名称：

  Aloisines, a New Family of CDK/GSK-3 Inhibitors. SAR Study, Crystal Structure in Complex with CDK2, Enzyme Selectivity, and Cellular Effects

  摘要：

  Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal functions, transcription, and exocytosis. The observation of CDK deregulations in various pathological situations suggests that CDK inhibitors may have a therapeutic value. In this article, we report on the identification of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a novel potent CDK inhibitory scaffold. A selectivity study performed on 26 kinases shows that aloisine A is highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3alpha/beta; the two latter enzymes have been implicated in Alzheimer's disease. Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. As observed with all inhibitors reported so far, aloisine interacts with the ATP-binding pocket through two hydrogen bonds with backbone nitrogen and oxygen atoms of Leu 83. Aloisine inhibits cell proliferation by arresting cells in both G1 and G2.

  DOI：

  10.1021/jm020319p

文献信息

• Pyrrolopyrazines as kinase inhibitors
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：EP1388541A1

  公开（公告）日：2004-02-11

  The invention relates to pyrrolo [2,3b]-pyrazine derivatives having the general formula (I) :    wherein : R2 and R3 are identical or different and represent H, C1-C6 alkyl, said alkyl being a straight or branched-chain alkyl, which can be substituted, R6 is an optionally substituted aromatic cycle Ar or a cycloalkyl, said cycloalkyl being optionally substituted by an aryl group which can also be substituted, R7 is H, C1-C6 alkyl, (alk.)n-hal., CH2-CH = CH2, CH2-cycloalkyl, CH2-Ar, with "alk." being a C1-C6 alkylene group, n being 1-6, Z is H or CH3. Application as active principle of pharmaceutical compositions, particularly for treating or preventing neurodegenerative disorders and proliferative disorders.

  该发明涉及具有一般式(I)的吡咯并[2,3b]-吡嗪衍生物：   其中：R2和R3相同或不同，代表H，C1-C6烷基，所述烷基为直链或支链烷基，可以被取代，R6是可选择被取代的芳香环Ar或环烷基，所述环烷基可被芳基取代，R7是H，C1-C6烷基，(烷基)n-卤，CH2-CH = CH2，CH2-环烷基，CH2-Ar，其中"烷基"是C1-C6烷基，n为1-6，Z为H或CH3。用作药物组合物的活性成分，特别用于治疗或预防神经退行性疾病和增殖性疾病。
• Compositions and methods for treating disorders associated with salt or fluid retention
  申请人：Ironwood Pharmaceuticals, Inc.

  公开号：EP2671584A2

  公开（公告）日：2013-12-11

  Methods for reducing the risk of or treating a disorder associated with fluid and/or salt retention in a patient are described. The methods include administering to the patient an agent selected from: a) an agent that reduces sodium absorption in the intestine; b) an agent that increases anion secretion in the intestine; or c) an agent that both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

  本文描述了降低患者发生与体液和/或盐潴留有关的疾病的风险或治疗这种疾病的方法。这些方法包括向患者施用选自以下几种的制剂：a) 减少肠道钠吸收的制剂；b) 增加肠道阴离子分泌的制剂；或 c) 既减少肠道钠吸收又增加肠道阴离子分泌的制剂。
• COMPOSITIONS AND METHODS FOR TREATING DISORDERS ASSOCIATED WITH SALT OR FLUID RETENTION
  申请人：Ironwood Pharmaceuticals, Inc.

  公开号：EP2152266A1

  公开（公告）日：2010-02-17
• Derivatives of Pyrrolo-Pyrazines Having a Kinase Inhibitory Activity and Their Biological Applications
  申请人：Meijer Laurent

  公开号：US20080161312A1

  公开（公告）日：2008-07-03

  The invention relates to pyrrolo[2,3b]-pyrazine derivatives having the general Formula (I) wherein R2 and R3 are identical or different and represent H, C1-C6 alkyl, said alkyl being a straight or branched-chain alkyl, which can be substituted, R6 is an optionally substituted aromatic cycle Ar or a cycloalkyl, said cycloalkyl being optionally substituted by an aryl group which can also be substituted, R7 is H, C1-C6 alkyl, (alk.)n-hal., CH2—CH═CH2, CH2-cycloalkyl, CH2—Ar, with “alk.” being a C1-C6 alkylene group, n being 1-6, Z is H or CH3. Application as active principle of pharmaceutical compositions, particularly for treating or preventing neurodegenerative disorders and proliferative disorders.
• Compositions and Methods for Treating Disorders Associated with Salt or Fluid Retention
  申请人：Currie Mark G.

  公开号：US20100215779A1

  公开（公告）日：2010-08-26

  Methods for reducing the risk of or treating a disorder associated with fluid and/or salt retention in a patient are described. The methods include administering to the patient an agent selected from: a) an agent that reduces sodium absorption in the intestine; b) an agent that increases anion secretion in the intestine; or c) an agent that both reduces sodium absorption in the intestine and increases anion secretion in the intestine.