3-(环丙烷磺酰胺)苯硼酸 | 1072945-67-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(环丙烷磺酰胺)苯硼酸
• 中文别名: 3-(环丙烷磺酰胺基)苯基硼酸
• 英文名称: 3-(Cyclopropanesulfonamido)phenylboronic acid
• 英文别名: [3-(cyclopropylsulfonylamino)phenyl]boronic acid
• CAS: 1072945-67-5
• 化学式: C₉H₁₂BNO₄S
• mdl: MFCD10699613
• 分子量: 241.076
• InChiKey: KOKPMJFSMXUSJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.79
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  95
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  6-chloro-3-(4-(methylsulfonyl)phenyl)imidazo[1,2-b]-pyridazine 、 3-(环丙烷磺酰胺)苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N-(3-(3-(4-(methylsulfonyl)phenyl)imidazo[1,2-b]pyridazin-6-yl)phenyl)cyclopropanesulfonamide
  参考文献：
  名称：

  Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1

  摘要：

  A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.

  DOI：

  10.1021/jm500098s

文献信息

• Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1
  作者：Claire Le Manach、Diego Gonzàlez Cabrera、Frederic Douelle、Aloysius T. Nchinda、Yassir Younis、Dale Taylor、Lubbe Wiesner、Karen L. White、Eileen Ryan、Corinne March、Sandra Duffy、Vicky M. Avery、David Waterson、Michael J. Witty、Sergio Wittlin、Susan A. Charman、Leslie J. Street、Kelly Chibale

  DOI：10.1021/jm500098s

  日期：2014.3.27

  A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.