N-cyclopropyl-N-((E)-4-hydroxycyclohexyl)-6-(piperidin-1-yl)picolinamide | 1346555-35-8

• 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: N-cyclopropyl-N-((E)-4-hydroxycyclohexyl)-6-(piperidin-1-yl)picolinamide
• CAS: 1346555-35-8
• 化学式: C₂₀H₂₉N₃O₂
• 分子量: 343.469
• InChiKey: JLYIRQFUBJUIOQ-QAQDUYKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  56.67
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  4-羟基环己酮乙二醇缩醛 在 盐酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成 N-cyclopropyl-N-((E)-4-hydroxycyclohexyl)-6-(piperidin-1-yl)picolinamide
  参考文献：
  名称：

  吡啶甲酰胺类强效抑制剂11β-羟类固醇脱氢酶（11β-HSD1）的合成和生物学评估

  摘要：

  描述了一系列6-取代的吡啶甲酰胺衍生物的合成及其对1β-11β-羟基类固醇脱氢酶的抑制活性。初始命中化合物的优化，ñ -环己基-6-（哌啶-1-基）吡啶甲酰胺（1从高吞吐量内部文库的筛选）导致高度有效的和代谢稳定的化合物的发现25，这是有效在小鼠离体药效学模型中降低剂量，并在口服后降低了HF / STZ小鼠模型中的空腹血糖和胰岛素水平。

  DOI：

  10.1016/j.bmcl.2014.11.074

文献信息

• 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：Sk Chemicals Co., Ltd.

  公开号：EP2566859B1

  公开（公告）日：2016-12-21
• US9096571B2
  申请人：——

  公开号：US9096571B2

  公开（公告）日：2015-08-04
• [EN] PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] COMPOSÉS DE PICOLINAMIDE ET DE PYRIMIDINE-4-CARBOXAMIDE, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT
  申请人：SK CHEMICALS CO LTD

  公开号：WO2011139107A2

  公开（公告）日：2011-11-10

  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 (LAD A), insulin tolerance syndromes, obesity, impaired glucose tolerane (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.
• Synthesis and biological evaluation of picolinamides as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
  作者：Je Ho Ryu、Shinae Kim、Hye Young Han、Hyun Joo Son、Hyun Jung Lee、Young Ah Shin、Jae-Sun Kim、Hyeung-geun Park

  DOI：10.1016/j.bmcl.2014.11.074

  日期：2015.2

  6-substituted picolinamide derivatives and their inhibitory activities against 11β-hydroxysteroid dehydrogenase type 1 are described. Optimization of the initial hit compound, N-cyclohexyl-6-(piperidin-1-yl)picolinamide (1) from high throughput screening of in-house library resulted in the discovery of the highly potent and metabolically stable compound 25, which was efficacious in a mouse ex vivo

  描述了一系列6-取代的吡啶甲酰胺衍生物的合成及其对1β-11β-羟基类固醇脱氢酶的抑制活性。初始命中化合物的优化，ñ -环己基-6-（哌啶-1-基）吡啶甲酰胺（1从高吞吐量内部文库的筛选）导致高度有效的和代谢稳定的化合物的发现25，这是有效在小鼠离体药效学模型中降低剂量，并在口服后降低了HF / STZ小鼠模型中的空腹血糖和胰岛素水平。