6-(4-bromophenyl)-5H-pyrrolo[2,3-b]pyrazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 6-(4-bromophenyl)-5H-pyrrolo[2,3-b]pyrazine
• 英文别名: 6-(4-bromophenyl)[5H]pyrrolo[2,3-b]pyrazine
• 化学式: C₁₂H₈BrN₃
• 分子量: 274.12
• InChiKey: ZIPGRNBNZKOCNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  2-甲基吡嗪 、 4-溴苯腈 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以24%的产率得到6-(4-bromophenyl)-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

• Azaindoles
  申请人：——

  公开号：US20040009983A1

  公开（公告）日：2004-01-15

  The invention is directed to compositions containing physiologically active compounds of general formula (I): 1 wherein R 1 is aryl or heteroaryl; R 2 represents hydrogen, acyl, cyano, halo, lower alkenyl or lower alkyl optionally substituted by a substituent selected from cyano, heteroaryl, heterocycloalkyl, —Z 1 R 8 , —C(═O)—NY 3 Y 4 , —CO 2 R 8 , —NY 3 Y 4 , —N(R 6 )—C(═O)—R 7 , —N(R 6 )—C(═O)—NY 3 Y 4 , —N(R 6 )—C(═O)—OR 7 , —N(R 6 )—SO 2 —R 7 , —N(R 6 )—SO 2 —NY 3 Y 4 and one or more halogen a toms ; R 3 represents hydrogen, aryl, cyano, halo, heteroaryl, lower alkyl, —C(═O)—OR 5 or —C(═O)—NY 3 Y; and X 1 represents N, CH, C-halo, C—CN, C—R 7 , C—NY 3 Y 4 , C—OH, C—Z 2 R 7 , C—C(═O)—OR 5 , C—C(═O)—NY 3 Y 4 , C—N(R 8 )—C(═O)—R 7 , C—SO 2 —NY 3 Y 4 , C—N(R 8 )—SO 2 —R 7 , C-alkenyl, C-alkynyl or C—NO 2 ; and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (I). Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit protein kinases.

  这项发明涉及含有一般式（I）中生理活性化合物的组合物：其中R1为芳基或杂芳基；R2代表氢、酰基、氰基、卤素、可选择地由氰基、杂芳基、杂环烷基、—Z1R8、—C（═O）—NY3Y4、—CO2R8、—NY3Y4、—N(R6)—C（═O）—R7、—N(R6)—C（═O）—NY3Y4、—N(R6)—C（═O）—OR7、—N(R6)—SO2—R7、—N(R6)—SO2—NY3Y4和一个或多个卤原子取代的较低烯基或较低烷基；R3代表氢、芳基、氰基、卤素、杂芳基、较低烷基、—C（═O）—OR5或—C（═O）—NY3Y；X1代表N、CH、C-卤素、C—CN、C—R7、C—NY3Y4、C—OH、C—Z2R7、C—C（═O）—OR5、C—C（═O）—NY3Y4、C—N(R8)—C（═O）—R7、C—SO2—NY3Y4、C—N(R8)—SO2—R7、C-烯基、C-炔基或C—NO2；以及它们的前药、这些化合物及其前药的药学上可接受的盐和溶剂，以及在一般式（I）范围内的新化合物。这些化合物和组合物具有有价值的药物特性，特别是抑制蛋白激酶的能力。
• 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。
• [EN] AZAINDOLES<br/>[FR] AZAINDOLES
  申请人：AVENTIS PHARMA LTD

  公开号：WO2003000688A1

  公开（公告）日：2003-01-03

  The invention is directed to physiologically active compounds of general formula (I): and compositions containing such compounds; and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (I). Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit kinases.

  该发明涉及具有通式（I）的生理活性化合物及含有这种化合物的组合物，以及这种化合物和它们的前药，以及这种化合物和它们的前药的药学上可接受的盐和溶剂化合物，以及在公式（I）范围内的新化合物。这些化合物和组合物具有有价值的药物特性，特别是抑制激酶的能力。
• AZAINDOLES
  申请人：Aventis Pharma Limited

  公开号：EP1263759B1

  公开（公告）日：2010-09-08
• HETEROCYCLIC N-OXIDES AS HYPOXIC SELECTIVE PROTEIN KINASE INHIBITORS
  申请人：Sentinel Oncology Limited

  公开号：EP1858883A2

  公开（公告）日：2007-11-28