tert-butyl (S)-(2-((5-bromopyridin-3-yl)oxy)-1-phenylethyl)carbamate | 552331-46-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl (S)-(2-((5-bromopyridin-3-yl)oxy)-1-phenylethyl)carbamate
• 英文别名: (2-hydroxy-1-phenyl-ethyl)-carbamic acid tert-butyl ester；(1S)-[2-(5-Bromo-pyridin-3-yloxy)-1-phenyl-ethyl]-carbamic Acid Tert-Butyl Ester；tert-butyl N-[(1S)-2-(5-bromopyridin-3-yl)oxy-1-phenylethyl]carbamate
• CAS: 552331-46-1
• 化学式: C₁₈H₂₁BrN₂O₃
• 分子量: 393.28
• InChiKey: UGZWUWQMCOTOFO-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(2-((5-bromopyridin-3-yl)oxy)-1-phenylethyl)carbamate 在 四(三苯基膦)钯 、 六甲基二锡 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (1S)-2-(5-isoquinolin-6-yl-pyridin-3-yloxy)-1-phenyl-ethylamine
  参考文献：
  名称：

  Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase

  摘要：

  Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure-activity relationship studies, and pharmacokinetic data are presented in this paper. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.046
• 作为产物：
  描述：

  N-(叔丁氧羰基)-L-2-苯甘氨酸 在 三苯基膦 、 偶氮二甲酸二乙酯 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 生成 tert-butyl (S)-(2-((5-bromopyridin-3-yl)oxy)-1-phenylethyl)carbamate
  参考文献：
  名称：

  Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase

  摘要：

  Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure-activity relationship studies, and pharmacokinetic data are presented in this paper. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.046

文献信息

• Kinase inhibitors
  申请人：——

  公开号：US20030187026A1

  公开（公告）日：2003-10-02

  Compounds having the formula 1 are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.

  具有以下化学式的化合物对抑制蛋白激酶很有用。还公开了抑制蛋白激酶的组合物以及在患者中抑制蛋白激酶的方法。
• Discovery of Novel <i>N</i>-(5-(Pyridin-3-yl)-1<i>H</i>-indazol-3-yl)benzamide Derivatives as Potent Cyclin-Dependent Kinase 7 Inhibitors for the Treatment of Autosomal Dominant Polycystic Kidney Disease
  作者：Bowen Yang、Haoran Zhang、Na Li、Lixin Gao、Hong Jiang、Weijuan Kan、Haoxing Yuan、Jia Li、Dongmei Zhao、Bing Xiong、Yubo Zhou、Dong Guo、Tongchao Liu

  DOI：10.1021/acs.jmedchem.2c01334

  日期：2022.12.8

  Madin–Darby canine kidney cyst model. In addition, compound B2 was also highly efficacious in suppressing renal cyst development in an ex vivo embryonic kidney cyst model and in vivo ADPKD mouse model. These results indicate that compound B2 represents a promising lead compound that deserves further investigation to discover novel therapeutic agents for ADPKD.

  最近的证据表明，CDK7 是常染色体显性多囊肾病 (ADPKD) 治疗的新型潜在药物靶点。在此，在结构分析的基础上，设计了具有新型支架的命中化合物3，并通过合理的设计策略进行了后续的药物化学工作，以提高 CDK7 抑制剂的效力和选择性。代表性化合物B2有效抑制 CDK7，IC 50值为 4 nM，并显示出对 CDK 的高选择性。在体外Madin-Darby 犬肾囊肿模型中，化合物B2显示出抑制囊肿生长的高效力，并且表现出比 THZ1 更低的细胞毒性。此外，化合物B2在体外胚胎肾囊肿模型和体内ADPKD 小鼠模型中抑制肾囊肿发展也非常有效。这些结果表明化合物B2代表了一种有前途的先导化合物，值得进一步研究以发现新的 ADPKD 治疗剂。
• US6831175B2
  申请人：——

  公开号：US6831175B2

  公开（公告）日：2004-12-14
• Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase
  作者：Sheela A. Thomas、Tongmei Li、Keith W. Woods、Xiaohong Song、Garrick Packard、John P. Fischer、Robert B. Diebold、Xuesong Liu、Yan Shi、Vered Klinghofer、Eric F. Johnson、Jennifer J. Bouska、Amanda Olson、Ran Guan、Shayna R. Magnone、Kennan Marsh、Yan Luo、Saul H. Rosenberg、Vincent L. Giranda、Qun Li

  DOI：10.1016/j.bmcl.2006.04.046

  日期：2006.7

  Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure-activity relationship studies, and pharmacokinetic data are presented in this paper. (c) 2006 Elsevier Ltd. All rights reserved.