1-BOC-吲哚-2-硼酸频那醇酯 | 1072944-96-7

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 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-BOC-吲哚-2-硼酸频那醇酯
• 中文别名: 1-BOC-吲哚-2-硼酸频哪醇酯；1-Boc-吲哚-2-硼酸频那醇酯
• 英文名称: tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate
• 英文别名: tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole-1-carboxylate
• CAS: 1072944-96-7
• 化学式: C₁₉H₂₆BNO₄
• 分子量: 343.231
• InChiKey: XHSKHKAKSUSKKP-UHFFFAOYSA-N

物化性质

• 沸点：
  454.6±37.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1-BOC-吲哚-2-硼酸频那醇酯 在 sodium carbonate 作用下， 以 1,3,5-三甲氧基苯 、 水 为溶剂， 反应 5.0h， 生成 1-Boc-吲哚
  参考文献：
  名称：

  A C–H Borylation Approach to Suzuki–Miyaura Coupling of Typically Unstable 2–Heteroaryl and Polyfluorophenyl Boronates

  摘要：

  A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used in situ. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids.

  DOI：

  10.1021/ol301570t
• 作为产物：
  描述：

  联硼酸频那醇酯 、 N-Boc-2-bromoindole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 二甲基亚砜 为溶剂， 生成 1-BOC-吲哚-2-硼酸频那醇酯
  参考文献：
  名称：

  基于结构的吲哚取代三唑并嘧啶设计作为用于治疗淋巴瘤的新型 EED–H3K27me3 抑制剂

  摘要：

  中断胚胎外胚层发育 (EED)–H3K27me3 相互作用是变构抑制多梳抑制复合物 2 (PRC2) 用于癌症治疗的一种很有前途的策略。在这项工作中，我们报告了新的基于三唑并嘧啶的 EED 抑制剂的基于结构的设计，其结构特征是 C8 位置的富电子吲哚环。特别是，ZJH-16 直接结合 EED（HTRF IC 50 = 2.72 nM，BLI K D = 4.4 nM）并有效抑制 KARPAS422 和 Pfeiffer 细胞的生长。在这两个细胞中，ZJH-16 选择性地与 EED 结合并降低 H3K27 三甲基化水平。ZJH-16 抑制 KARPAS422 细胞中 PRC2 的基因沉默功能。ZJH-16 具有良好的药代动力学 (PK) 特性和出色的口服生物利用度 (F = 94.7%)。更重要的是，ZJH-16在口服给药后在KARPAS422异种移植模型中显示出强劲的肿瘤消退，肿瘤生长抑制达到近100%。ZJH-16

  DOI：

  10.1021/acs.jmedchem.2c02028

文献信息

• Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models
  作者：Ulrich Lücking、Lars Wortmann、Antje M. Wengner、Julien Lefranc、Philip Lienau、Hans Briem、Gerhard Siemeister、Ulf Bömer、Karsten Denner、Martina Schäfer、Marcus Koppitz、Knut Eis、Florian Bartels、Benjamin Bader、Wilhelm Bone、Dieter Moosmayer、Simon J. Holton、Uwe Eberspächer、Joanna Grudzinska-Goebel、Christoph Schatz、Gesa Deeg、Dominik Mumberg、Franz von Nussbaum

  DOI：10.1021/acs.jmedchem.0c00369

  日期：2020.7.9

  instability, selective ATR inhibition has been recognized as a promising new approach in cancer therapy. We now report the identification and preclinical evaluation of the novel, clinical ATR inhibitor BAY 1895344. Starting from quinoline 2 with weak ATR inhibitory activity, lead optimization efforts focusing on potency, selectivity, and oral bioavailability led to the discovery of the potent, highly selective

  ATR激酶通过激活DNA损伤修复的基本信号通路，特别是对复制压力的响应，在DNA损伤应答中起关键作用。由于DNA损伤和复制压力是基因组不稳定的主要来源，因此选择性ATR抑制已被认为是癌症治疗中一种有希望的新方法。现在，我们报告新颖的临床ATR抑制剂BAY 1895344的鉴定和临床前评估。从喹啉2开始由于ATR抑制活性较弱，针对效价，选择性和口服生物利用度的前导优化工作导致发现了有效的，高选择性的，口服的ATR抑制剂BAY 1895344，在携带某些DNA损伤的癌症异种移植模型中显示出强大的单一疗法功效维修缺陷。此外，BAY 1895344与某些诱导DNA损伤的化学疗法联合治疗可产生协同的抗肿瘤活性。BAY 1895344目前正在对晚期实体瘤和淋巴瘤（NCT03188965）的患者进行临床研究。
• Hydrogenation of Borylated Arenes
  作者：Marco Wollenburg、Daniel Moock、Frank Glorius

  DOI：10.1002/anie.201810714

  日期：2019.5.13

  abundant aryl boronic acids and their derivatives catalyzed by rhodium cyclic (alkyl)(amino)carbene (Rh–CAAC) is reported. The reaction tolerates a variety of boron‐protecting groups and provides direct access to a broad scope of saturated, borylated carbo‐ and heterocycles with various functional groups. The transformation is strategically important because the versatile saturated boronate products are

  据报道，环状（烷基）（氨基）卡宾铑（Rh–CAAC）催化了丰富的芳基硼酸及其衍生物的顺式选择性氢化。该反应可耐受各种硼保护基，并可以直接进入具有各种官能团的各种饱和，硼化的碳环和杂环。该转变在战略上很重要，因为通用的饱和硼酸酯产品很难用其他方法制备。硼基的后官能化证明了饱和环状结构单元的效用。
• COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
  申请人：Charrier Jean-Damien

  公开号：US20120040020A1

  公开（公告）日：2012-02-16

  The present disclosure relates to pyrazine compounds of formula I: wherein L, n, R 1 , and R 2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.

  本公开涉及式I的吡嗪化合物：其中L、n、R1和R2如规范所述。这些化合物可用作ATR蛋白激酶的抑制剂。本公开还涉及包含本公开化合物的药学上可接受的组合物；使用本公开化合物治疗各种疾病、障碍和病况的方法；制备本公开化合物的过程；制备本公开化合物的中间体；以及在体外应用中使用这些化合物的方法，例如研究生物和病理现象中的激酶、这些激酶介导的细胞内信号传导途径的研究以及新的激酶抑制剂的比较评估。
• Compounds useful as inhibitors of ATR kinase
  申请人：Charrier Jean-Damien

  公开号：US08410112B2

  公开（公告）日：2013-04-02

  The present disclosure relates to pyrazine compounds of formula I: wherein L, n, R1, and R2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.

  本公开涉及式I的吡嗪化合物：其中L、n、R1和R2如说明书所述。这些化合物可用作ATR蛋白激酶的抑制剂。本公开还涉及包括本公开化合物的药学上可接受的组合物；使用本公开化合物治疗各种疾病、疾病和病况的方法；制备本公开化合物的过程；制备本公开化合物的中间体；以及在体外应用中使用化合物的方法，例如研究生物和病理现象中的激酶，介导这些激酶的细胞内信号转导途径的研究以及新激酶抑制剂的比较评估。
• [EN] ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF CANCER<br/>[FR] INHIBITEURS CHROMÉNONE ALLOSTÉRIQUES DE LA PHOSPHOINOSITIDE 3-KINASE (PI3K) POUR LE TRAITEMENT DU CANCER
  申请人：PETRA PHARMA CORP

  公开号：WO2022251482A1

  公开（公告）日：2022-12-01

  The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3‑kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I): (I) or pharmaceutically acceptable salts thereof wherein R, R1, R2,R3, R4, R5, R6, R7, and R8, are as defined herein. The disclosure also relates to methods of making and using compounds of Formula (I) or pharmaceutically acceptable salts thereof.

  本公开涉及公式（I）的化合物，作为磷脂酰肌醇3-激酶（PI3K）的变构异构酮抑制剂，用于治疗与PI3K调节相关的疾病或疾病，其中公式（I）：（I）或其药学上可接受的盐，其中R，R1，R2，R3，R4，R5，R6，R7和R8如本文所定义。本公开还涉及制备和使用公式（I）或其药学上可接受的盐的方法。