N-(1-adamantyl)-N',N'-(1,5-pentamethylenediyl)urea

• 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: N-(1-adamantyl)-N',N'-(1,5-pentamethylenediyl)urea
• 英文别名: N-(1-adamantyl)piperidine-1-carboxamide
• 化学式: C₁₆H₂₆N₂O
• 分子量: 262.395
• InChiKey: FYCNPTBHADGOQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  1-哌啶酰氯 、 盐酸金刚烷胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以31%的产率得到N-(1-adamantyl)-N',N'-(1,5-pentamethylenediyl)urea
  参考文献：
  名称：

  Novel 11β-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the introduction of an oxygen atom in the adamantane scaffold

  摘要：

  The adamantane scaffold is found in several marketed drugs and in many investigational 11 beta-HSD1 inhibitors. Interestingly, all the clinically approved adamantane derivatives are C-1 substituted. We demonstrate that, in a series of paired adamantane isomers, substitution of the adamantane in C-2 is preferred over the substitution at C-1 and is necessary for potency at human 11 beta-HSD1. Furthermore, the introduction of an oxygen atom in the hydrocarbon scaffold of adamantane is deleterious to 11 beta-HSD1 inhibition. Molecular modeling studies provide a basis to rationalize these features. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.097

文献信息

• Pd(OAc)₂-Catalyzed Carbonylation of Amines
  作者：Kazuhiko Orito、Mamoru Miyazawa、Takatoshi Nakamura、Akiyoshi Horibata、Harumi Ushito、Hideo Nagasaki、Motoki Yuguchi、Satoshi Yamashita、Tetsuro Yamazaki、Masao Tokuda

  DOI：10.1021/jo060612n

  日期：2006.8.1

  phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In

  无膦的催化体系[Pd（OAc）2 -Cu（OAc）2-空气]在沸腾的甲苯中，在CO气体（1个大气压）下引发了胺的底物特异性羰基化。通过伯胺的羰基化获得对称的N，N'-二烷基脲。N，N，N′-三烷基脲通过向上述反应容器中添加仲胺而选择性地形成。仲胺不产生四烷基脲。但是，在烷基链上带有苯基的二烷基胺，例如N-对单烷基化的苄胺或苯乙胺衍生物进行直接的芳族羰基化反应，得到五元或六元的苯并内酰胺。在羰基化反应中，发现Pd（II）与邻位钯的间位取代基之间的螯合效应或位阻以及羰基化之前形成的环钯的产物的环大小可产生良好的位点选择性并提高反应速率。相反，具有羟基的ω-芳基烷基胺的羰基化既不产生脲也没有苯并内酰胺，而是平稳地产生1，3-恶唑烷酮。在所用条件下，胺的盐酸盐也进行羰基化，得到相应的酰胺。该程序使得可以制备氨基酸酯的脲和实际收率的N-烷基氨基甲酸酯。
• 2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors
  申请人：Merck Sante

  公开号：EP1801098A1

  公开（公告）日：2007-06-27

  The present invention relates to 2-adamantylurea derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

  本发明涉及公式I的2-金刚烷基脲衍生物，作为选择性抑制酶11-β-羟基类固醇脱氢酶1（11β-HSD1）的药物，并利用这些化合物治疗和预防代谢综合征、糖尿病、胰岛素抵抗、肥胖、脂质紊乱、青光眼、骨质疏松症、认知障碍、焦虑、抑郁、免疫紊乱、高血压以及其他疾病和症状。
• 2-ADAMANTYLUREA DERIVATIVES AS SELECTIVE 11BETA-HSD1 INHIBITORS
  申请人：Carniato Denis

  公开号：US20090227631A1

  公开（公告）日：2009-09-10

  The present invention relates to 2-adamantylurea derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

  本发明涉及式I的2-金刚烷基脲衍生物，作为选择性抑制酶11-β-羟基类固醇脱氢酶1型（11β-HSD1）的抑制剂及其在代谢综合征、糖尿病、胰岛素抵抗、肥胖、脂质紊乱、青光眼、骨质疏松症、认知障碍、焦虑、抑郁、免疫障碍、高血压和其他疾病和病况的治疗和预防中的应用。
• 2-ADAMANTYLUREA DERIVATIVES AS SELECTIVE 11B-HSD1 INHIBITORS
  申请人：CARNIATO Denis

  公开号：US20120172396A1

  公开（公告）日：2012-07-05

  The present invention relates to 2-adamantylurea derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

  本发明涉及式I的2-金刚烷基脲衍生物，作为选择性抑制酶11-β-羟基类固醇脱氢酶1型（11β-HSD1）的抑制剂，并且利用这些化合物治疗和预防代谢综合征、糖尿病、胰岛素抵抗、肥胖症、脂质紊乱、青光眼、骨质疏松症、认知障碍、焦虑症、抑郁症、免疫障碍、高血压和其他疾病和病况。
• US8188288B2
  申请人：——

  公开号：US8188288B2

  公开（公告）日：2012-05-29