benzyl 2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate | 1237517-82-6

• 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: benzyl 2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
• 英文别名: benzyl 2-phenylmethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
• CAS: 1237517-82-6
• 化学式: C₂₇H₂₉BO₅
• 分子量: 444.335
• InChiKey: DEEKXRRBWXZXFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.92
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate 在 potassium fluoride 、 copper diacetate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 5-[(3R)-3-methylmorpholin-4-yl]-2-phenylmethoxy-N-pyridazin-4-ylbenzamide
  参考文献：
  名称：

  5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy

  摘要：

  We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18 proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following intravenous infusion at 5 mg/kg/h.

  DOI：

  10.1016/j.bmcl.2018.11.054
• 作为产物：
  描述：

  5-溴水杨酸 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 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 benzyl 2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
  参考文献：
  名称：

  5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy

  摘要：

  We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18 proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following intravenous infusion at 5 mg/kg/h.

  DOI：

  10.1016/j.bmcl.2018.11.054

文献信息

• N-ACYL ANTHRANILIC ACID DERIVATIVE OR SALT THEREOF
  申请人：Yokotani Junichi

  公开号：US20110275797A1

  公开（公告）日：2011-11-10

  An N-acyl anthranilic acid derivative represented by general formula (1) or a salt thereof is useful for prevention or treatment of diseases associated with excessive production of collagen. (In the formula, R 1 represents a carboxyl group or the like; R 2 represents a hydrogen atom or the like; R 3 represents an optionally substituted aryl group or the like; X 1 represents a carbonyl group; X 2 represents a bonding hand; X 3 represents a bonding hand; X 4 represents a bonding hand or the like; and A represents an optionally substituted phenyl group or the like.)

  通用公式（1）表示的N-酰基蒽酸衍生物或其盐对预防或治疗与胶原蛋白过度产生相关的疾病具有用处。（在该公式中，R1代表羧基或类似物；R2代表氢原子或类似物；R3代表可选择取代的芳基或类似物；X1代表羰基；X2代表连接手；X3代表连接手；X4代表连接手或类似物；A代表可选择取代的苯基或类似物。）
• N-acyl anthranilic acid derivative or salt thereof
  申请人：Yokotani Junichi

  公开号：US08492582B2

  公开（公告）日：2013-07-23

  The invention relates to an N-acyl anthranilic acid derivative or it's salt having collagen production inhibitory action.

  本发明涉及一种具有胶原蛋白生成抑制作用的N-酰基蒽酰氨酸衍生物或其盐。
• 5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy
  作者：Xiao Ding、Luigi Piero Stasi、Xuedong Dai、Kai Long、Cheng Peng、Baowei Zhao、Hailong Wang、Changhui Sun、Huan Hu、Zehong Wan、Karamjit S. Jandu、Oliver J. Philps、Yan Chen、Lizhen Wang、Qian Liu、Colin Edge、Yi Li、Kelly Dong、Xiaoming Guan、F. David Tattersall、Alastair D. Reith、Feng Ren

  DOI：10.1016/j.bmcl.2018.11.054

  日期：2019.1

  We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18 proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following intravenous infusion at 5 mg/kg/h.