ethyl 3-[2-(2-bromo-1-triethylsilanyloxyethyl)-pyridin-3-yl]-propionate | 864829-68-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 3-[2-(2-bromo-1-triethylsilanyloxyethyl)-pyridin-3-yl]-propionate
• 英文别名: ethyl 3-[2-(2-bromo-1-triethylsilanyloxyethyl)pyridin-3-yl]propionate；Ethyl 3-[2-(2-bromo-1-triethylsilyloxyethyl)pyridin-3-yl]propanoate
• CAS: 864829-68-5
• 化学式: C₁₈H₃₀BrNO₃Si
• 分子量: 416.431
• InChiKey: DVAXAIGAMXVWFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-[2-(2-bromo-1-triethylsilanyloxyethyl)-pyridin-3-yl]-propionate 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 1.92h， 以7.44 g的产率得到ethyl (6RS,8SR)-8-[(triethylsilyl)oxy]-5.6.7.8-tetrahydroquinoline-6-carboxylate
  参考文献：
  名称：

  A Novel Class of Cycloalkano[b]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K⁺Channel

  摘要：

  A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+ channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.

  DOI：

  10.1021/jm701590h
• 作为产物：
  描述：

  2-氯-3-吡啶甲醛 在 四(三苯基膦)钯 咪唑 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 硼烷四氢呋喃络合物 、 sodium hydride 、 copper(l) chloride 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.33h， 生成 ethyl 3-[2-(2-bromo-1-triethylsilanyloxyethyl)-pyridin-3-yl]-propionate
  参考文献：
  名称：

  EP1726590

  摘要：

  公开号：

文献信息

• EP1726590
  申请人：——

  公开号：——

  公开（公告）日：——
• A Novel Class of Cycloalkano[<i>b</i>]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K⁺Channel
  作者：Takashi Yoshizumi、Hirobumi Takahashi、Hiroshi Miyazoe、Yuichi Sugimoto、Tomohiro Tsujita、Tetsuya Kato、Hirokatsu Ito、Hiroshi Kawamoto、Mioko Hirayama、Daisuke Ichikawa、Tomoko Azuma-Kanoh、Satoshi Ozaki、Yoshihiro Shibata、Takeshi Tani、Masato Chiba、Yasuyuki Ishii、Shoki Okuda、Kiyoshi Tadano、Takahiro Fukuroda、Osamu Okamoto、Hisashi Ohta

  DOI：10.1021/jm701590h

  日期：2008.7

  A series of compounds based on 7-[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+ channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.