6-氰基-4-吲哚硼酸酯 | 955979-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 6-氰基-4-吲哚硼酸酯
• 英文名称: 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carbonitrile
• CAS: 955979-23-4
• 化学式: C₁₅H₁₇BN₂O₂
• 分子量: 268.123
• InChiKey: GZHUWMIKULBEKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  58
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-fluoro-4-(2-methanesulfonyl-6-morpholin-4-yl-pyrimidin-4-yl)-1H-indole 、 6-氰基-4-吲哚硼酸酯 生成 4-(2-methanesulfonyl-6-morpholin-4-yl-pyrimidin-4-yl)-1H-indole-6-carbonitrile
  参考文献：
  名称：

  PYRIMIDINE DERIVATIVES AS INHIBITORS OF PHOSPHATIDYLINOSITOL-3-KINASE

  摘要：

  本发明提供了一种嘧啶化合物，其化学式为(I)，其中R1、R2和Y具有本文所定义的任何值；或其药学上可接受的盐。这些化合物是PI3K的抑制剂，因此可用于治疗由PI3激酶引起的异常细胞生长、功能或行为所导致的疾病和障碍，如癌症、免疫障碍、心血管疾病、病毒感染、炎症、代谢/内分泌功能障碍和神经系统疾病。

  公开号：

  US20100130496A1
• 作为产物：
  描述：

  4-溴-1H-吲哚-6-甲腈 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以76%的产率得到6-氰基-4-吲哚硼酸酯
  参考文献：
  名称：

  [EN] TRICYCLIC HETEROCYCLIC COMPOUNDS AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES TRICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE

  摘要：

  这项发明涉及到式I的化合物：(I)或其药学上可接受的盐和/或立体异构体。该发明的化合物在治疗中是有用的。

  公开号：

  WO2017029521A1

文献信息

• Thienopyrimidine derivatives as P13K inhibitors
  申请人：F. Hoffmann-La Roche AG

  公开号：US08293735B2

  公开（公告）日：2012-10-23

  Thienopyrimidines of formula (I) wherein W and R1 to R4 are as defined in the claims, and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PI3 kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

  公式（I）中W和R1至R4的定义如权利要求中所述，其药学上可接受的盐是PI3K的抑制剂，并且对于p110δ异构体具有选择性，该异构体是Ia类PI3激酶，优于其他Ia类和Ib类激酶。这些化合物可用于治疗由于PI3激酶引起的异常细胞生长，功能或行为而引起的疾病和障碍，如癌症，免疫障碍，心血管疾病，病毒感染，炎症，代谢/内分泌功能障碍和神经系统障碍。
• THIENOPYRIMIDINE DERIVATIVES AS P13K INHIBITORS
  申请人：Hancox Timothy Colin

  公开号：US20110021496A1

  公开（公告）日：2011-01-27

  Thienopyrimidines of formula (I) wherein W and R 1 to R 4 are as defined in the claims, and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PI3 kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

  公式（I）中，W和R1至R4的定义如索权所述，其药学上可接受的盐是PI3K的抑制剂，并且选择性地作用于p110δ同工酶，该同工酶是一种Ia类PI3激酶，优于其他Ia类和Ib类激酶。这些化合物可用于治疗由PI3激酶引起的异常细胞生长、功能或行为所引起的疾病和障碍，如癌症、免疫障碍、心血管疾病、病毒感染、炎症、代谢/内分泌功能障碍和神经系统障碍。
• [EN] THIENOPYRIMIDIENE DERIVATIVES AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS DE THIÉNOPYRIMIDIÈNE COMME INHIBITEURS DE PI3K
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009053715A8

  公开（公告）日：2010-06-03
• Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition
  作者：Brian S. Safina、Stewart Baker、Matt Baumgardner、Paul M. Blaney、Bryan K. Chan、Yung-Hsiang Chen、Matthew W. Cartwright、Georgette Castanedo、Christine Chabot、Arnaud J. Cheguillaume、Paul Goldsmith、David M. Goldstein、Bindu Goyal、Timothy Hancox、Raj K. Handa、Pravin S Iyer、Jasmit Kaur、Rama Kondru、Jane R. Kenny、Sussie L. Krintel、Jun Li、John Lesnick、Matthew C. Lucas、Cristina Lewis、Sophie Mukadam、Jeremy Murray、Alan J. Nadin、Jim Nonomiya、Fernando Padilla、Wylie S. Palmer、Jodie Pang、Neil Pegg、Steve Price、Karin Reif、Laurent Salphati、Pascal A. Savy、Eileen M. Seward、Stephen Shuttleworth、Sukhjit Sohal、Zachary K. Sweeney、Suzanne Tay、Parcharee Tivitmahaisoon、Bohdan Waszkowycz、Binqing Wei、Qin Yue、Chenghong Zhang、Daniel P. Sutherlin

  DOI：10.1021/jm3003747

  日期：2012.6.28

  PI3K delta is a lipid kinase and a member of a larger family of enzymes, PI3K class IA(alpha, beta, delta) and IB (gamma), which catalyze the phosphorylation of PIP2 to PIP3. PI3K delta is mainly expressed in leukocytes, where it plays a critical, nonredundant role in B cell receptor mediated signaling and provides an attractive opportunity to treat diseases where B cell activity is essential, e.g., rheumatoid arthritis. We report the discovery of novel, potent, and selective PI3K delta inhibitors and describe a structural hypothesis for isoform (alpha, beta, gamma) selectivity gained from interactions in the affinity pocket. The critical component of our initial pharmacophore for isoform selectivity was strongly associated with CYP3A4 time-dependent inhibition (TDI). We describe a variety of strategies and methods for monitoring and attenuating TDI. Ultimately, a structure-based design approach was employed to identify a suitable structural replacement for further optimization.
• [EN] TRICYCLIC HETEROCYCLIC COMPOUNDS AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES TRICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE
  申请人：KARUS THERAPEUTICS LTD

  公开号：WO2017029521A1

  公开（公告）日：2017-02-23

  The invention relates to a compound of formula I: (I) or a pharmaceutically acceptable salt thereof and/or stereoisomers thereof. The compounds of the invention are useful in therapy.

  这项发明涉及到式I的化合物：(I)或其药学上可接受的盐和/或立体异构体。该发明的化合物在治疗中是有用的。