(+)-4-(2-methylphenyl)-1-{(7R)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl}piperidine | 1039359-46-0

• 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: (+)-4-(2-methylphenyl)-1-{(7R)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl}piperidine
• 英文别名: (7'R)-7'-[[4-(2-methylphenyl)piperidin-1-yl]methyl]spiro[1,3-dioxolane-2,9'-5,6,7,8-tetrahydrocyclohepta[b]pyridine]
• CAS: 1039359-46-0
• 化学式: C₂₅H₃₂N₂O₂
• 分子量: 392.541
• InChiKey: DKEDARRBVROCEZ-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  34.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-4-(2-methylphenyl)-1-{(7R)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl}piperidine 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (-)-4-(2-methylphenyl)-1-{(7R)-[9-oxo-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-7-yl]methyl}piperidine
  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：

  4-(2-甲基苯基)哌啶盐酸盐 、 (+)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl 4-methylbenzenesulfonate 在 三乙胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (+)-4-(2-methylphenyl)-1-{(7R)-5,6,7,8-tetrahydrospiro[cyclohepta[b]pyridine-9,2'-[1,3]dioxolan]-7-ylmethyl}piperidine
  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

文献信息

• 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.