2-(4-(2-(5,6-dimethoxypyridin-3-yl)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-1H-pyrazol-1-yl)-2-methylpropanenitrile | 1315538-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(4-(2-(5,6-dimethoxypyridin-3-yl)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-1H-pyrazol-1-yl)-2-methylpropanenitrile
• 英文别名: 2-[4-[2-(5,6-dimethoxypyridin-3-yl)-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]pyrazol-1-yl]-2-methylpropanenitrile
• CAS: 1315538-59-0
• 化学式: C₂₁H₂₀N₆O₃
• 分子量: 404.428
• InChiKey: YIBINECYRPENGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 2-methylpyridine-3-carboxylate 在 四(三苯基膦)钯 、 三氯异氰尿酸 、 sodium carbonate 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 84.0h， 生成 2-(4-(2-(5,6-dimethoxypyridin-3-yl)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-1H-pyrazol-1-yl)-2-methylpropanenitrile
  参考文献：
  名称：

  Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS)

  摘要：

  The lipid kinase phosphoinositide 3-kinase gamma (PI3K gamma) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3K gamma, we discovered a series of aza-isoindolinones as selective, brain penetrant inhibitors of PI3K gamma. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.8b00085

文献信息

• ISOINDOLINONE INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE
  申请人：Aronov Alex

  公开号：US20120040950A1

  公开（公告）日：2012-02-16

  The present invention relates to compounds useful as inhibitors of PI3K, particularly of PI3Kγ. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及用作PI3K抑制剂的化合物，特别是PI3Kγ的抑制剂。本发明还提供包含该化合物的药学上可接受的组合物，并提供使用该组合物治疗各种疾病、病况或疾病的方法。
• Isoindolinone inhibitors of phosphatidylinositol 3-kinase
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US10183933B2

  公开（公告）日：2019-01-22

  The present invention relates to compounds useful as inhibitors of PI3K, particularly of PI3Kγ. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及可用作 PI3K（尤其是 PI3Kγ）抑制剂的化合物。本发明还提供了包含所述化合物的药学上可接受的组合物，以及使用该组合物治疗各种疾病、病症或失调的方法。
• US8466288B2
  申请人：——

  公开号：US8466288B2

  公开（公告）日：2013-06-18
• US9676759B2
  申请人：——

  公开号：US9676759B2

  公开（公告）日：2017-06-13
• Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS)
  作者：Jon H. Come、Philip N. Collier、James A. Henderson、Albert C. Pierce、Robert J. Davies、Arnaud Le Tiran、Hardwin O’Dowd、Upul K. Bandarage、Jingrong Cao、David Deininger、Ron Grey、Elaine B. Krueger、Derek B. Lowe、Jianglin Liang、Yusheng Liao、David Messersmith、Suganthi Nanthakumar、Emmanuelle Sizensky、Jian Wang、Jinwang Xu、Elaine Y. Chin、Veronique Damagnez、John D. Doran、Wojciech Dworakowski、James P. Griffith、Marc D. Jacobs、Suvarna Khare-Pandit、Sudipta Mahajan、Cameron S. Moody、Alex M. Aronov

  DOI：10.1021/acs.jmedchem.8b00085

  日期：2018.6.28

  The lipid kinase phosphoinositide 3-kinase gamma (PI3K gamma) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3K gamma, we discovered a series of aza-isoindolinones as selective, brain penetrant inhibitors of PI3K gamma. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.