2-(2-fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | 1510828-68-8

• 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: 2-(2-fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• 英文别名: 2-(2-Fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 1510828-68-8
• 化学式: C₁₃H₁₇BFNO₄
• 分子量: 281.092
• InChiKey: VJFYRTJYOVWHNP-UHFFFAOYSA-N

物化性质

• 沸点：
  363.7±42.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

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：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  64.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-(5-amino-2-fluoro-4-methylphenyl)-2-methyl-2H-pyridazin-3-one
  参考文献：
  名称：

  Novel Series of Dihydropyridinone P2X7 Receptor Antagonists

  摘要：

  Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5", and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.

  DOI：

  10.1021/acs.jmedchem.5b00365
• 作为产物：
  描述：

  联硼酸频那醇酯 、 4-溴-5-氟-2-硝基甲苯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 生成 2-(2-fluoro-4-methyl-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
  参考文献：
  名称：

  结构-活性关系（SAR）优化6-（吲哚-2-基）吡啶-3-磺酰胺：靶向丙型肝炎（HCV）NS4B的有力，选择性和口服生物利用度的小分子的鉴定

  摘要：

  一种新型的，靶向NS4B丙型肝炎RNA复制的强效，和口服生物抑制剂，化合物4吨（PTC725），已经通过6-（吲哚-2-基）的化学优化吡啶-3-磺酰胺标识2，以改善DMPK和安全特性。SAR研究的重点是确定吲哚N-1，C-5和C-6位置的取代基与磺酰胺基的最佳组合，以限制体内氧化代谢的潜力并达到可接受的药代动力学轮廓。化合物4t具有抗HCV 1b复制子的出色效能，相对于细胞GAPDH ，EC 50 = 2 nM，选择性指数> 5000。复合4t 具有总体良好的药代动力学特征，大鼠，狗和猴子的口服生物利用度分别为62％，78％和18％，并且大鼠的肝血浆接触比为25，具有良好的组织分布特性。

  DOI：

  10.1021/jm401621g

文献信息

• Structure–Activity Relationship (SAR) Optimization of 6-(Indol-2-yl)pyridine-3-sulfonamides: Identification of Potent, Selective, and Orally Bioavailable Small Molecules Targeting Hepatitis C (HCV) NS4B
  作者：Nanjing Zhang、Xiaoyan Zhang、Jin Zhu、Anthony Turpoff、Guangming Chen、Christie Morrill、Song Huang、William Lennox、Ramesh Kakarla、Ronggang Liu、Chunshi Li、Hongyu Ren、Neil Almstead、Srikanth Venkatraman、F. George Njoroge、Zhengxian Gu、Valerie Clausen、Jason Graci、Stephen P. Jung、Yingcong Zheng、Joseph M. Colacino、Fred Lahser、Josephine Sheedy、Anna Mollin、Marla Weetall、Amin Nomeir、Gary M. Karp

  DOI：10.1021/jm401621g

  日期：2014.3.13

  an acceptable pharmacokinetic profile. Compound 4t has excellent potency against the HCV 1b replicon, with an EC50 = 2 nM and a selectivity index of >5000 with respect to cellular GAPDH. Compound 4t has an overall favorable pharmacokinetic profile with oral bioavailability values of 62%, 78%, and 18% in rats, dogs, and monkeys, respectively, as well as favorable tissue distribution properties with a

  一种新型的，靶向NS4B丙型肝炎RNA复制的强效，和口服生物抑制剂，化合物4吨（PTC725），已经通过6-（吲哚-2-基）的化学优化吡啶-3-磺酰胺标识2，以改善DMPK和安全特性。SAR研究的重点是确定吲哚N-1，C-5和C-6位置的取代基与磺酰胺基的最佳组合，以限制体内氧化代谢的潜力并达到可接受的药代动力学轮廓。化合物4t具有抗HCV 1b复制子的出色效能，相对于细胞GAPDH ，EC 50 = 2 nM，选择性指数> 5000。复合4t 具有总体良好的药代动力学特征，大鼠，狗和猴子的口服生物利用度分别为62％，78％和18％，并且大鼠的肝血浆接触比为25，具有良好的组织分布特性。
• Novel Series of Dihydropyridinone P2X7 Receptor Antagonists
  作者：Francisco Lopez-Tapia、Keith A. M. Walker、Christine Brotherton-Pleiss、Joanie Caroon、Dov Nitzan、Lee Lowrie、Shelley Gleason、Shu-Hai Zhao、Jacob Berger、Debra Cockayne、Deborah Phippard、Rebecca Suttmann、William L. Fitch、David Bourdet、Pankaj Rege、Xiaojun Huang、Scott Broadbent、Charles Dvorak、Jiang Zhu、Paul Wagner、Fernando Padilla、Brad Loe、Alam Jahangir、André Alker

  DOI：10.1021/acs.jmedchem.5b00365

  日期：2015.11.12

  Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5", and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.