5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-hydroxybenzoic acid | 1237518-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-hydroxybenzoic acid
• 英文别名: 5-{1-[(Tert-butoxy)carbonyl]piperidin-4-yl}-2-hydroxybenzoic acid；2-hydroxy-5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]benzoic acid
• CAS: 1237518-10-3
• 化学式: C₁₇H₂₃NO₅
• 分子量: 321.373
• InChiKey: CWLCHLLCQAYFHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-hydroxybenzoic acid 在 盐酸 、 potassium carbonate 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 7.0h， 生成 benzyl 2-(benzyloxy)-5-(piperidin-4-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
• 作为产物：
  描述：

  tert-butyl 4-(4-(benzyloxy)-3-((benzyloxy)carbonyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、344.75 kPa 条件下， 以84%的产率得到5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-hydroxybenzoic acid
  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。）
• US8492582B2
  申请人：——

  公开号：US8492582B2

  公开（公告）日：2013-07-23
• [EN] N-ACYL ANTHRANILIC ACID DERIVATIVE OR SALT THEREOF<br/>[FR] DÉRIVÉ DE L'ACIDE N-ACYLE ANTHRANILIQUE OU SON SEL
  申请人：TOYAMA CHEMICAL CO LTD

  公开号：WO2010087430A1

  公开（公告）日：2010-08-05

  一般式「式中、Ｒ１は、カルボキシル基などを；Ｒ２は、水素原子などを；Ｒ３は、置換されていてもよいアリール基などを；Ｘ１は、カルボニル基を；Ｘ２は、結合手を；Ｘ３は、結合手を；Ｘ４は、結合手などを；Ａは、置換されていてもよいフェニル基などを示す。」で表されるＮ－アシルアントラニル酸誘導体またはその塩は、コラーゲンの過剰産生が関与する疾患の予防または治療などの処置に有用である。
• 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.