1-(叔丁基二甲基)-5-氟-4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吲哚 | 1148004-02-7

• 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: 1-(叔丁基二甲基)-5-氟-4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吲哚
• 英文名称: 5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tert-butyldimethylsilylindole
• 英文别名: 1-(tert-butyldimethylsilyl)-5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole；tert-butyl-[5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indol-1-yl]-dimethylsilane
• CAS: 1148004-02-7
• 化学式: C₂₀H₃₁BFNO₂Si
• 分子量: 375.367
• InChiKey: OAMAAQPCABOWNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  23.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  1-(叔丁基二甲基)-5-氟-4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吲哚 在 四(三苯基膦)钯 、 palladium diacetate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 为溶剂， 生成 4-[4-(5-fluoro-1H-indol-4-yl)-7-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-2-yl]morpholine
  参考文献：
  名称：

  FUSED PYRIMIDINE COMPOUND, INTERMEDIATE, PREPARATION METHOD THEREFOR, AND COMPOSITION AND APPLICATION THEREOF

  摘要：

  揭示了一种融合嘧啶化合物，其中间体，制备方法以及其组成和应用。本发明提供了一种如式I所示的融合嘧啶化合物，该化合物的药用可接受盐，水合物，溶剂合物，以及光学异构体或前药。本发明还提供了应用式I所示的融合嘧啶化合物，药用可接受盐，水合物，溶剂合物，以及该化合物的光学异构体或前药在制备用于治疗和/或预防激酶相关疾病的药物中。本发明的融合嘧啶化合物I是一种高效的PI3激酶抑制剂，可用于制备用于预防和/或治疗细胞增殖性疾病，如癌症，感染，炎症和自身免疫疾病的药物。

  公开号：

  US20160214994A1
• 作为产物：
  描述：

  频哪醇 、 1-(tert-butyldimethylsilyl)-5-fluoro-1H-indole 在 四甲基乙二胺 、 仲丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 2.0h， 以71%的产率得到1-(叔丁基二甲基)-5-氟-4-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吲哚
  参考文献：
  名称：

  Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition

  摘要：

  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.

  DOI：

  10.1021/jm3003747

文献信息

• IMIDAZOPYRAZINES FOR USE AS KINASE INHIBITORS
  申请人：Pastor Fernández Joaquin

  公开号：US20120083492A1

  公开（公告）日：2012-04-05

  There is provided compounds of formula (I), wherein R 1 , R 2 , R 3 , R 4 and R 5 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

  提供了式(I)的化合物，其中R1、R2、R3、R4和R5在描述中有给定的含义，以及它们的药用可接受的酯、酰胺、溶剂合物或盐，这些化合物在治疗需要或期望抑制蛋白质或脂质激酶（例如PI3-K和/或mTOR）的疾病方面非常有用，特别是在治疗癌症或增生性疾病方面。
• Use of P13K Inhibitors for the Treatment of Obesity, Steatosis and ageing
  申请人：Serrano Marugan Manuel

  公开号：US09993554B2

  公开（公告）日：2018-06-12

  The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and/or uncoupling protein 1 (Thermogenin/Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

  该发明的第一个方面涉及一种磷脂酰肌醇3-激酶抑制剂，用于治疗或预防与棕色脂肪细胞中过氧化物酶体增殖物激活受体γ共激活因子1-α（Pgd1α）和/或解偶联蛋白1（热原蛋白/Ucp1）表达相关的疾病或病况。该疾病或病况可能与正能量失衡相关，例如肥胖、肥胖相关疾病或病况、脂肪肝和生物老化（性能老化）。该发明的另一个方面提供了使用磷脂酰肌醇3-激酶抑制剂促进个体体重减轻的方法。
• PYRIDO[3,2-d]PYRIMIDINE PI3K DELTA INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20110207713A1

  公开（公告）日：2011-08-25

  Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I化合物，包括立体异构体、几何异构体、互变异构体、代谢物和药学上可接受的盐，对于抑制PI3K的δ异构体以及治疗通过脂质激酶介导的疾病如炎症、免疫疾病和癌症非常有用。本文介绍了使用公式I化合物的方法，用于哺乳动物细胞中的体外、体内诊断、预防或治疗这些疾病或相关病理条件。
• Pyrido[3,2-d]pyrimidine PI3K delta inhibitor compounds and methods of use
  申请人：Genetech, Inc.

  公开号：US08563540B2

  公开（公告）日：2013-10-22

  Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I化合物，包括立体异构体、几何异构体、互变异构体、代谢产物和药学上可接受的盐，可用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，如炎症、免疫性疾病和癌症。本文披露了使用公式I化合物进行哺乳动物细胞中的体内、体外和原位诊断、预防或治疗此类疾病或相关病理状况的方法。
• FUSED PYRIMIDINE COMPOUND, INTERMEDIATE, PREPARATION METHOD THEREFOR, AND COMPOSITION AND APPLICATION THEREOF
  申请人：SHANGHAI YINGLI PHARMACEUTICAL CO., LTD

  公开号：US20160214994A1

  公开（公告）日：2016-07-28

  Disclosed are a fused pyrimidine compound, an intermediate, a preparation method therefor, and a composition and an application thereof. The present invention provides a fused pyrimidine compound shown in formula I, pharmaceutically acceptable salt, hydrate, solvate, and an optical isomer or prodrug of the compound. The present invention further provides applications of the fused pyrimidine compound shown in formula I, the pharmaceutically acceptable salt, the hydrate, solvate, and the optical isomer or the prodrug of the compound in the preparing drugs for curing and/or preventing a kinase-related disease. The fused pyrimidine compound I of the present invention is an efficient PI3 kinase depressor, and can be used to prepare drugs for preventing and/or curing cell-proliferation diseases such as cancer, infection, inflammation, and an autoimmune disease.

  揭示了一种融合嘧啶化合物，其中间体，制备方法以及其组成和应用。本发明提供了一种如式I所示的融合嘧啶化合物，该化合物的药用可接受盐，水合物，溶剂合物，以及光学异构体或前药。本发明还提供了应用式I所示的融合嘧啶化合物，药用可接受盐，水合物，溶剂合物，以及该化合物的光学异构体或前药在制备用于治疗和/或预防激酶相关疾病的药物中。本发明的融合嘧啶化合物I是一种高效的PI3激酶抑制剂，可用于制备用于预防和/或治疗细胞增殖性疾病，如癌症，感染，炎症和自身免疫疾病的药物。