tert-butyl 3-(2-bromophenoxy)piperidine-1-carboxylate | 444605-65-6

• 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: tert-butyl 3-(2-bromophenoxy)piperidine-1-carboxylate
• 英文别名: 3-(2-bromo-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester
• CAS: 444605-65-6
• 化学式: C₁₆H₂₂BrNO₃
• 分子量: 356.26
• InChiKey: IATACTDWNSGNTE-UHFFFAOYSA-N

物化性质

• 沸点：
  414.4±35.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2-bromophenoxy)piperidine-1-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 tert-butyl 3-(2-(2-((6-cyanopyridin-3-yl)amino)pyrimidin-5-yl)phenoxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies

  摘要：

  Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule. (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 mu M) and displayed low affinity for hERG (IC50> 40 mu M). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.03.062
• 作为产物：
  描述：

  N-BOC-3-羟基哌啶 在 4-二甲氨基吡啶 、 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 tert-butyl 3-(2-bromophenoxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies

  摘要：

  Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule. (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 mu M) and displayed low affinity for hERG (IC50> 40 mu M). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.03.062

文献信息

• Piperazine- and piperidine-derivatives as melanocortin receptor agonists
  申请人：——

  公开号：US20040082590A1

  公开（公告）日：2004-04-29

  The present invention relates to melanocortin receptor agonists of formula I, which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction. 1

  本发明涉及公式I的黑素皮质素受体激动剂，可用于治疗肥胖症、糖尿病以及男性和/或女性性功能障碍。
• PIPERAZINE- AND PIPERIDINE-DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1370558A1

  公开（公告）日：2003-12-17
• US7186715B2
  申请人：——

  公开号：US7186715B2

  公开（公告）日：2007-03-06
• [EN] PIPERAZINE- AND PIPERIDINE-DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS<br/>[FR] DERIVES DE PIPERAZINE ET DE PIPERIDINE EN TANT QU'AGONISTES DU RECEPTEUR DE LA MELANOCORTINE
  申请人：LILLY CO ELI

  公开号：WO2002059117A1

  公开（公告）日：2002-08-01

  The present invention relates to melanocortin receptor agonists of formula I,which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction.
• Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies
  作者：Lexian Tong、Pinrao Song、Kailong Jiang、Lei Xu、Tingting Jin、Peipei Wang、Xiaobei Hu、Sui Fang、Anhui Gao、Yubo Zhou、Tao Liu、Jia Li、Yongzhou Hu

  DOI：10.1016/j.ejmech.2019.03.062

  日期：2019.7

  Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule. (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 mu M) and displayed low affinity for hERG (IC50> 40 mu M). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies. (C) 2019 Published by Elsevier Masson SAS.