(6-bromopyridin-2-yl)(4-methylpiperidin-1-yl)methanone | 912935-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (6-bromopyridin-2-yl)(4-methylpiperidin-1-yl)methanone
• 英文别名: (6-bromopyridin-2-yl)-(4-methylpiperidin-1-yl)methanone
• CAS: 912935-68-3
• 化学式: C₁₂H₁₅BrN₂O
• 分子量: 283.168
• InChiKey: WQKFKMZTDOYSBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  哌啶 、 (6-bromopyridin-2-yl)(4-methylpiperidin-1-yl)methanone 在 tris-(dibenzylideneacetone)dipalladium(0) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以80%的产率得到(4-methylpiperidin-1-yl)(6-(piperidin-1-yl)pyridin-2-yl)methanone
  参考文献：
  名称：

  [EN] PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] COMPOSÉS DE PICOLINAMIDE ET DE PYRIMIDINE-4-CARBOXAMIDE, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT

  摘要：

  公开号：

  WO2011139107A3
• 作为产物：
  描述：

  4-甲基哌啶 、 6-溴-2-吡啶羧酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以97%的产率得到(6-bromopyridin-2-yl)(4-methylpiperidin-1-yl)methanone
  参考文献：
  名称：

  [EN] PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] COMPOSÉS DE PICOLINAMIDE ET DE PYRIMIDINE-4-CARBOXAMIDE, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT

  摘要：

  公开号：

  WO2011139107A3

文献信息

• Inhibitors of 11-beta hydroxysteroid dehydrogenase type I
  申请人：Li J, James

  公开号：US20060235028A1

  公开（公告）日：2006-10-19

  Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein G, L, Q, Z, R 6 , R 7 , and R 8 are defined herein.

  提供了一种新的化合物，它们是11-β-羟基类固醇脱氢酶I型抑制剂。11-β-羟基类固醇脱氢酶I型抑制剂在治疗、预防或减缓需要11-β-羟基类固醇脱氢酶I型抑制剂治疗的疾病的进展方面是有用的。这些新的化合物具有以下结构：或其立体异构体或前药或其药用可接受的盐，其中G、L、Q、Z、R6、R7和R8在此处定义。
• INHIBITORS OF 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I
  申请人：Li James J.

  公开号：US20110077395A1

  公开（公告）日：2011-03-31

  Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein G, L, Q, Z, R 6 , R 7 , and R 8 are defined herein.

  提供了新的化合物，它们是11-β-羟基类固醇脱氢酶I抑制剂。11-β-羟基类固醇脱氢酶I抑制剂在治疗、预防或减缓需要11-β-羟基类固醇脱氢酶I抑制剂治疗的疾病方面是有用的。这些新的化合物具有以下结构：或其立体异构体或前药或其药学上可接受的盐，其中G、L、Q、Z、R6、R7和R8在此定义。
• PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Ryu Je Ho

  公开号：US20130210811A1

  公开（公告）日：2013-08-15

  Provided are picolinamide and pyrimidine-4-carboxamide compounds, a method for preparing the same, a pharmaceutical composition containing the same, and a medical use using the compound as an agent for preventing, regulating, and treating diseases related to regulation of glucocorticoids by using selective inhibitory activity of the compound for an 11β-HSD1 enzyme. The picolinamide and pyrimidine-4-carboxamide compounds of the present invention are selective inhibitors of human-derived 11β-HSD1 enzymes, and are useful in an agent for preventing, regulating, and treating diseases related to glucocorticoid regulation in which human-derived 11β-HSD1 enzymes are involved, for example, metabolic syndromes such as, type 1 and type 2 diabetes, diabetes later complications, latent autoimmune diabetes adult (LADA), insulin tolerance syndromes, obesity, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.

  本发明提供了吡啶甲酰胺和嘧啶-4-羧酰胺化合物、制备方法、含有该化合物的制药组合物以及使用该化合物作为11β-HSD1酶的选择性抑制剂，用于预防、调节和治疗与糖皮质激素调节相关的疾病的医疗用途。本发明的吡啶甲酰胺和嘧啶-4-羧酰胺化合物是人源11β-HSD1酶的选择性抑制剂，可用于预防、调节和治疗与人源11β-HSD1酶参与的糖皮质激素调节相关疾病，例如代谢综合征，如1型和2型糖尿病、糖尿病后并发症、成人隐形自身免疫性糖尿病（LADA）、胰岛素耐受综合征、肥胖症、糖耐量受损（IGT）、空腹血糖受损（IFG）、糖耐量受损、血脂异常、动脉粥样硬化、高血压等。
• Picolinamide and pyrimidine-4-carboxamide compounds, process for preparing and pharmaceutical composition comprising the same
  申请人：Ryu Je Ho

  公开号：US09096571B2

  公开（公告）日：2015-08-04

  Provided are picolinamide and pyrimidine-4-carboxamide compounds, a method for preparing the same, a pharmaceutical composition containing the same, and a medical use using the compound as an agent for preventing, regulating, and treating diseases related to regulation of glucocorticoids by using selective inhibitory activity of the compound for an 11β-HSD1 enzyme. The picolinamide and pyrimidine-4-carboxamide compounds of the present invention are selective inhibitors of human-derived 11β-HSD1 enzymes, and are useful in an agent for preventing, regulating, and treating diseases related to glucocorticoid regulation in which human-derived 11β-HSD1 enzymes are involved, for example, metabolic syndromes such as, type 1 and type 2 diabetes, diabetes later complications, latent autoimmune diabetes adult (LADA), insulin tolerance syndromes, obesity, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.

  本发明提供了吡啶甲酰胺和嘧啶-4-羧酰胺化合物、其制备方法、含有该化合物的药物组合物，以及使用该化合物作为11β-HSD1酶的选择性抑制活性的药剂来预防、调节和治疗与糖皮质激素调节相关的疾病的医疗用途。本发明的吡啶甲酰胺和嘧啶-4-羧酰胺化合物是人源11β-HSD1酶的选择性抑制剂，在预防、调节和治疗与人源11β-HSD1酶相关的糖皮质激素调节疾病中非常有用，例如代谢综合征、1型和2型糖尿病、糖尿病后并发症、成人潜在自身免疫性糖尿病、胰岛素耐量综合征、肥胖症、糖耐量受损、空腹血糖受损、糖耐量受损、血脂异常、动脉硬化和高血压等。
• Pyridine amides as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1
  作者：Haixia Wang、Zheming Ruan、James J. Li、Ligaya M. Simpkins、Rebecca A. Smirk、Shung C. Wu、Robert D. Hutchins、David S. Nirschl、Katy Van Kirk、Christopher B. Cooper、James C. Sutton、Zhengping Ma、Rajasree Golla、Ramakrishna Seethala、Mary Ellen K. Salyan、Akbar Nayeem、Stanley R. Krystek、Steven Sheriff、Daniel M. Camac、Paul E. Morin、Brian Carpenter、Jeffrey A. Robl、Robert Zahler、David A. Gordon、Lawrence G. Hamann

  DOI：10.1016/j.bmcl.2008.04.069

  日期：2008.6

  Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series.