4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane | 1367127-40-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane
• 英文别名: 4,4,5,5-Tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane；4,4,5,5-tetramethyl-2-[4-[4-(trifluoromethyl)phenoxy]phenyl]-1,3,2-dioxaborolane
• CAS: 1367127-40-9
• 化学式: C₁₉H₂₀BF₃O₃
• 分子量: 364.172
• InChiKey: KWELKLMDYNYJMK-UHFFFAOYSA-N

物化性质

• 沸点：
  402.8±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane 在 bis-triphenylphosphine-palladium(II) chloride 盐酸 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 15.5h， 生成 methyl 4-chloro-6-(4-(4-(trifluoromethyl)phenoxy)phenyl)picolinate
  参考文献：
  名称：

  [EN] PYRIDINE COMPOUNDS AND THE USES THEREOF
  [FR] COMPOSÉS DE PYRIDINE ET SES UTILISATIONS

  摘要：

  公开号：

  WO2012035421A3
• 作为产物：
  描述：

  对氯三氟甲苯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium tert-butylate 、 potassium acetate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.33h， 生成 4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat.

  DOI：

  10.1021/jm501608q

文献信息

• Discovery of 4,7-Diamino-5-(4-phenoxyphenyl)-6-methylene-pyrimido[5,4-<i>b</i>]pyrrolizines as Novel Bruton’s Tyrosine Kinase Inhibitors
  作者：Yu Xue、Peiran Song、Zilan Song、Aoli Wang、Linjiang Tong、Meiyu Geng、Jian Ding、Qingsong Liu、Liping Sun、Hua Xie、Ao Zhang

  DOI：10.1021/acs.jmedchem.8b00441

  日期：2018.5.24

  An alternative medicinal chemistry approach was conducted on Bruton’s tyrosine kinase (BTK) inhibitor 1 (ibrutinib) by merging the pyrazolo[3,4-d]pyrimidine component into a tricyclic skeleton. Two types of compounds were prepared, and their biochemical activities on BTK as well as stereochemistry effects were determined. Structural optimization focusing on the reactive binding group to BTK Cys481

  通过将吡唑并[3,4- d ]嘧啶组分合并成三环骨架，对布鲁顿酪氨酸激酶（BTK）抑制剂1（依鲁替尼）进行了另一种药物化学处理。制备了两种类型的化合物，并确定了它们对BTK的生化活性以及立体化学作用。进行了结构优化，重点是与BTK Cys481的反应性结合基团和以代谢研究为指导的代谢位点。7S被认为是最有效的，对BTK的IC 50值为0.4 nM，对BTK依赖的TMD8细胞的IC 50为16 nM。相比1，7S对B细胞受体信号通路的抑制作用强一些。在源自TMD8细胞的动物异种移植模型中，7S在15 mg / kg QD剂量下显示出5.3的相对肿瘤体积，在25 mg / kg QD较高剂量下比1（RTV 6.6）更有效。所有这些结果表明7S是一种值得进一步分析的新型BTK抑制剂。
• [EN] PYRIMIDINES AND USE THEREOF<br/>[FR] PYRIMIDINES ET LEUR UTILISATION
  申请人：PURDUE PHARMA LP

  公开号：WO2015094443A1

  公开（公告）日：2015-06-25

  The present disclosure provides pyrimidines of Formula I: and pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, G, Y, n, R2a, R2b, and R3 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I and the pharmaceutically acceptable salts and solvates thereof to treat a disorder responsive to the blockade of one or more sodium channels. In one embodiment, compounds of the present disclosure are useful for treating pain.

  本公开提供了式I的嘧啶类化合物及其药用可接受的盐和溶剂化合物，其中A1、X、A2、G、Y、n、R2a、R2b和R3的定义如规范中所述。本公开还涉及使用式I的化合物以及其药用可接受的盐和溶剂化合物来治疗对一种或多种钠通道阻滞有反应的疾病。在一种实施例中，本公开的化合物对治疗疼痛具有用处。
• [EN] PYRIMIDINE CARBOXAMIDES AS SODIUM CHANNEL BLOCKERS<br/>[FR] PYRIMIDINE CARBOXAMIDES À TITRE DE BLOQUEURS DES CANAUX SODIQUES
  申请人：PURDUE PHARMA LP

  公开号：WO2014135955A1

  公开（公告）日：2014-09-12

  The present disclosure provides substituted pyrimidine carboxamides of Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

  本公开提供了公式（I）的取代嘧啶羧酰胺及其在药学上可接受的盐和溶剂化合物，其中A1、X、A2、W1、W2、W3、E、Z和R4的定义如规范中所述。本公开还涉及使用公式（I）的化合物治疗对钠通道阻断有反应的疾病。本公开的化合物特别适用于治疗疼痛。
• [EN] PYRIMIDINES AS SODIUM CHANNEL BLOCKERS<br/>[FR] PYRIMIDINES UTILISÉES COMME BLOQUEURS DE CANAUX SODIQUES
  申请人：PURDUE PHARMA LP

  公开号：WO2013030665A1

  公开（公告）日：2013-03-07

  The present disclosure provides substituted pyrimidine compounds of Formula (I), and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

  本公开提供了式（I）的取代嘧啶化合物，以及其药用可接受的盐、前药和溶剂化合物，其中A1、X、A2、W1、W2、W3、E、Z和R4的定义如规范中所述。本公开还涉及使用式（I）的化合物来治疗对钠通道阻滞有响应的疾病。本公开的化合物特别适用于治疗疼痛。
• PYRIMIDINES AS SODIUM CHANNEL BLOCKERS
  申请人：PURDUE PHARMA L.P.

  公开号：US20140303139A1

  公开（公告）日：2014-10-09

  The present disclosure provides substituted pyrimidine compounds of Formula (I), and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A 1 , X, A 2 , W 1 , W 2 , E, Z, and R 4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

  本公开提供式（I）的取代嘧啶化合物，以及其药学上可接受的盐、前药和溶剂化物，其中A1、X、A2、W1、W2、E、Z和R4的定义如规范中所述。本公开还涉及使用式（I）的化合物治疗对钠通道阻滞响应的疾病。本公开的化合物特别适用于治疗疼痛。