N,N-bisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine | 1400668-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N,N-bisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine
• 英文别名: N,N-bis(tert-butoxycarbonyl) 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine；tert-butyl N-[(tert-butoxy)carbonyl]-N-[6-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate；tert-butyl N-[(2-methylpropan-2-yl)oxycarbonyl]-N-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate
• CAS: 1400668-06-5
• 化学式: C₂₀H₃₂BN₃O₆
• 分子量: 421.302
• InChiKey: MPDGREDXDDKJJG-UHFFFAOYSA-N

物化性质

• 沸点：
  504.6±60.0 °C (Predicted,Press: 760 Torr)
• 密度：
  1.15±0.1 g/cm³ (Predicted,Temp: 20 °C; Press: 760 Torr)
• pKa：
  0.76±0.10 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N-bisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 碳酸氢钠 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 17.0h， 生成 tert-butyl (6-(4-(3-cyano-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)pyrazin-2-yl)carbamate
  参考文献：
  名称：

  [EN] TANK-BINDING KINASE INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DE KINASES SE LIANT À TANK

  摘要：

  揭示了具有以下化学式（I）的化合物及其使用和制备方法。

  公开号：

  WO2015187684A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 potassium acetate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 N,N-bisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine
  参考文献：
  名称：

  Lanraplenib（GS-9876）的发现：一种用于自身免疫性疾病的每日一次的脾酪氨酸激酶抑制剂。

  摘要：

  脾酪氨酸激酶（SYK）是多种免疫细胞类型（例如B细胞，单核细胞和巨噬细胞）中信号传导的关键调节剂。因此，已经进行了许多努力来鉴定选择性抑制SYK的化合物作为治疗自身免疫和炎性疾病的手段。我们先前披露了GS-9973（entospletinib）作为一种选择性SYK抑制剂，正在血液系统恶性肿瘤的临床评估中。但是，BID给药方案以及与质子泵抑制剂（PPI）的药物相互作用阻止了恩斯普替尼在炎性疾病中的发展。在此，我们报告了第二代SYK抑制剂GS-9876（lanraplenib）的发现，该药物具有适合于每天一次给药且与PPI无任何相互作用的人药代动力学特性。

  DOI：

  10.1021/acsmedchemlett.9b00621

文献信息

• [EN] COMPOUNDS AND THEIR USES AS SPLEEN TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS EN TANT QU'INHIBITEURS DE LA TYROSINE KINASE DE LA RATE
  申请人：NANJING RUIJIE PHARMA CO LTD

  公开号：WO2021244430A1

  公开（公告）日：2021-12-09

  Provided are compounds of Formula (I) which can be used as Syk inhibitors and potently as therapeutic agents against diseases mediated by Syk.

  提供了式（I）的化合物，可用作Syk抑制剂，并且在通过Syk介导的疾病中作为治疗剂具有强大的作用。
• Syk 억제제
  申请人：GILEAD SCIENCES, INC. 길리애드 사이언시즈, 인코포레이티드(519990290219)

  公开号：KR20160037198A

  公开（公告）日：2016-04-05

  본 개시내용은 Syk 억제제인 화합물, 및 암 및 염증성 상태를 비롯한 다양한 질환 상태의 치료에서의 그의 용도에 관한 것이다. 특정한 실시양태에서, 화합물의 구조는 하기 화학식 I로 주어진다. 003c#화학식 I003e# 상기 식에서, X, X, X, R, R, R, R, 및 Y는 본원에 기재된 바와 같다. 본 개시내용은 화학식 I의 화합물 또는 그의 제약상 허용되는 염을 포함하는 제약 조성물, 및 Syk에 의해 매개되는 상태를 치료하기 위해 이들 화합물 및 조성물을 사용하는 방법을 추가로 제공한다.

  This text appears to be a scientific or technical document discussing the therapeutic uses of a compound called Syk inhibitor in the treatment of various conditions including cancer and inflammatory diseases. It also mentions the chemical structure of the compound given by the chemical formula I. In the formula, X, X, X, R, R, R, R, and Y are as described in the specification. The document further provides methods for using these compounds and compositions containing compounds or salts thereof of the chemical formula I to treat conditions mediated by Syk.
• NOVEL PYRIDOPYRIMIDINE DERIVATIVES AND USE THEREOF
  申请人：Lee Gilnam

  公开号：US20120238587A1

  公开（公告）日：2012-09-20

  The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.

  该发明提供了由化学式I表示的新型取代吡啶嘧啶化合物或其药用可接受的盐、溶剂合物、多型体、酯、互变异构体或前药，以及包含这些化合物的组合物。所提供的化合物可用作磷脂酰肌醇3′ OH激酶家族（PI3K）的抑制剂，用于治疗炎症性疾病、癌症、心血管疾病、过敏、哮喘和自身免疫性疾病。
• [EN] SYK INHIBITORS<br/>[FR] INHIBITEURS DE SYK
  申请人：GILEAD SCIENCES INC

  公开号：WO2016010809A1

  公开（公告）日：2016-01-21

  The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease slates, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk. In certain embodiments, also disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof.

  本公开涉及一类Syk抑制剂化合物及其在治疗各种疾病状态中的应用，包括癌症和炎症性疾病。具体实施例中，该化合物的结构由公式I给出：其中R1、R2、R3和R4如本文所述。本公开还提供包括公式I化合物或其药学上可接受的盐的药物组合物，以及使用这些化合物和组合物治疗Syk介导的疾病的方法。在某些实施例中，还公开了治疗患有癌症的受试者（例如人类）的方法，包括向受试者施用一定量的公式I化合物或其药学上可接受的盐，与长春碱类药物或其药学上可接受的盐结合。
• SYK INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20150175616A1

  公开（公告）日：2015-06-25

  The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R 1 , R 2 , R 3 , and R 4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

  本公开涉及一种用于治疗各种疾病状态的Syk抑制剂化合物，包括癌症和炎症性疾病。在特定实施例中，化合物的结构由式I给出：其中R1、R2、R3和R4如本文所述。本公开还提供了包括式I化合物或其药学上可接受的盐或共晶体的药物组合物，以及使用这些化合物和组合物治疗由Syk介导的疾病的方法。