ethyl (2E)-4-{[(4-iodo-1H-pyrrol-2-yl)carbonyl]amino}but-2-enoate | 1218810-47-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (2E)-4-{[(4-iodo-1H-pyrrol-2-yl)carbonyl]amino}but-2-enoate
• 英文别名: ethyl (E)-4-[(4-iodo-1H-pyrrole-2-carbonyl)amino]but-2-enoate
• CAS: 1218810-47-9
• 化学式: C₁₁H₁₃IN₂O₃
• 分子量: 348.14
• InChiKey: QNGOSUZWPMFMQJ-ONEGZZNKSA-N

物化性质

• 沸点：
  501.8±50.0 °C(Predicted)
• 密度：
  1.659±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (2E)-4-{[(4-iodo-1H-pyrrol-2-yl)carbonyl]amino}but-2-enoate 在 lithium hydroxide monohydrate 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 42.5h， 生成 N-(2,2-dimethylpropyl)-2-{1-oxo-7-[4-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}acetamide
  参考文献：
  名称：

  Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases

  摘要：

  A novel series of PIM inhibitors was derived from a combined effort in natural product-inspired library generation and screening. The novel pyrrolo[1,2-a]pyrazinones initial hits are inhibitors of PIM isoforms with IC50 values in the low micromolar range. The application of a rational optimization strategy, guided by the determination of the crystal structure of the complex in the kinase domain of PIM1 with compound 1, led to the discovery of compound 15a, which is a potent PIM kinases inhibitor exhibiting excellent selectivity against a large panel of kinases, representative of each family. The synthesis, structure-activity relationship studies, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Furthermore, the cellular activities including inhibition of cell growth and modulation of downstream targets are also described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.054
• 作为产物：
  描述：

  4-溴巴豆酸乙酯 在 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 ethyl (2E)-4-{[(4-iodo-1H-pyrrol-2-yl)carbonyl]amino}but-2-enoate
  参考文献：
  名称：

  Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases

  摘要：

  A novel series of PIM inhibitors was derived from a combined effort in natural product-inspired library generation and screening. The novel pyrrolo[1,2-a]pyrazinones initial hits are inhibitors of PIM isoforms with IC50 values in the low micromolar range. The application of a rational optimization strategy, guided by the determination of the crystal structure of the complex in the kinase domain of PIM1 with compound 1, led to the discovery of compound 15a, which is a potent PIM kinases inhibitor exhibiting excellent selectivity against a large panel of kinases, representative of each family. The synthesis, structure-activity relationship studies, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Furthermore, the cellular activities including inhibition of cell growth and modulation of downstream targets are also described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.054

文献信息

• [EN] 3,4 DIHYDRO-2H-PYRROLO[1,2-a]PYRAZIN-1-ONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 3,4-DIHYDRO-2H-PYRROLO[1,2-A]PYRAZINE-1-ONE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2010031816A1

  公开（公告）日：2010-03-25

  Compounds which are 4,7-disubstituted derivatives of3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one compounds, or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

  该专利涉及一类4,7-二取代的3,4-二氢-2H-吡咯并[1,2-a]吡嗪-1-酮化合物，或其药用盐，以及它们的制备方法和包含它们的药物组合物；这些化合物可用于治疗由蛋白激酶活性改变引起和/或相关的疾病，如癌症、病毒感染、预防艾滋病毒感染者中的艾滋病发展、细胞增殖异常、自身免疫和神经退行性疾病；此外，还公开了一种在固相合成条件下制备本发明化合物的方法以及包含多种化合物的化学文库。
• 3,4-DIHYDRO-2H-PYRROLO[1,2-a]PYRAZIN-1-ONE DERIVATIVES
  申请人：Mirizzi Danilo

  公开号：US20110251179A1

  公开（公告）日：2011-10-13

  Compounds which are 4,7-disubstituted derivatives of 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one compounds, or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

  本发明揭示了3,4-二氢-2H-吡咯并[1,2-a]吡嗪-1-酮化合物的4,7-二取代衍生物，或其药学上可接受的盐，以及它们的制备方法和包括它们的制药组合物；这些化合物在治疗由改变的蛋白激酶活性引起和/或相关的疾病中具有用途，例如癌症、病毒感染、预防HIV感染个体的艾滋病发展、细胞增殖性疾病、自身免疫和神经退行性疾病；本发明还揭示了一种在固相合成条件下制备本发明化合物和包括其多个的化学库的方法。
• 3,4-DIHYDRO-2H-PYRROLO[1,2-A]PYRAZIN-1-ONE DERIVATIVES FOR THE MODULATION OF THE ACTIVITY OF PROTEIN KINASES
  申请人：Mirizzi Danilo

  公开号：US20130137696A1

  公开（公告）日：2013-05-30

  Compounds which are 4,7-disubstituted derivatives of 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one compounds, or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

  本发明揭示了3,4-二氢-2H-吡咯并[1,2-a]吡嗪-1-酮化合物的4,7-二取代衍生物，或其药学上可接受的盐，以及它们的制备方法和包含它们的制药组合物；这些化合物在治疗由改变的蛋白激酶活性引起和/或与之相关的疾病中有用，例如癌症、病毒感染、预防HIV感染个体中的艾滋病发展、细胞增殖性疾病、自身免疫和神经退行性疾病；本发明还揭示了一种在固相合成条件下制备本发明化合物和包含多个化合物的化学文库的方法。
• 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one derivatives for the modulation of the activity of protein kinases
  申请人：Mirizzi Danilo

  公开号：US08394802B2

  公开（公告）日：2013-03-12

  Compounds which are 4,7-disubstituted derivatives of 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one compounds with the formula or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

  本发明揭示了式为4,7-二取代衍生物的3,4-二氢-2H-吡咯并[1,2-a]吡嗪-1-酮化合物或其药学上可接受的盐，其制备过程和包含它们的制药组合物；这些化合物在治疗由改变的蛋白激酶活性引起和/或相关的疾病中有用，如癌症、病毒感染、预防HIV感染个体的艾滋病发展、细胞增殖性疾病、自身免疫和神经退行性疾病；本发明还揭示了一种在固相合成条件下制备本发明化合物和包含多个化合物的化学库的方法。
• Substituted 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-ones as modulators of protein kinase activity
  申请人：Mirizzi Danilo

  公开号：US08981092B2

  公开（公告）日：2015-03-17

  Compounds which are 4,7-disubstituted derivatives of 3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one compounds, or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

  本发明揭示了3,4-二氢-2H-吡咯并[1,2-a]吡嗪-1-酮化合物的4,7-二取代衍生物或其医药上可接受的盐，其制备过程和包含它们的制药组合物；这些化合物对治疗由改变的蛋白激酶活性引起和/或相关的疾病如癌症，病毒感染，预防HIV感染者发展艾滋病，细胞增殖性疾病，自身免疫和神经退行性疾病等非常有用；本发明还揭示了一种在固相合成条件下制备本发明化合物和包含多个这些化合物的化学库的方法。