N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-4-carboxamide | 180136-42-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-4-carboxamide
• CAS: 180136-42-9
• 化学式: C₂₂H₂₇N₃O₂
• 分子量: 365.475
• InChiKey: NXOILVZSAWPUQE-UHFFFAOYSA-N

物化性质

• 沸点：
  508.4±45.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-4-carboxamide 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 6.0h， 以53%的产率得到N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]-1-oxidopyridin-1-ium-4-carboxamide
  参考文献：
  名称：

  New Low-Density Lipoprotein Receptor Upregulators Acting via a Novel Mechanism

  摘要：

  The synthesis and biological activity of a new series of benzamides and related compounds that upregulate the expression of the low-density lipoprotein (LDL) receptor in human hepatocytes (HepG2 cells) by a novel mechanism are described. The lead compound, N-[5-[(3-cyclohexylpropionyl)amino]-2-methylphenyl]-4-hydroxybenzamide (1, RPR102359), increased the expression of the LDL receptors in HepG2 cells by 80% when tested at a concentration of 3 mu M. Mevinolin (lovastatin) was found to increase the LDL receptor expression by 70% at the same concentration. In contrast to mevinolin, 1 was found to have no effect on cholesterol biosynthesis in liver homogenates or in HepG2 cells at doses where substantial upregulation of the LDL receptor was observed and thus stimulated LDL receptor expression by a novel mechanism.

  DOI：

  10.1021/jm960153q
• 作为产物：
  描述：

  3-环己基丙酰氯 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 生成 N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-4-carboxamide
  参考文献：
  名称：

  New Low-Density Lipoprotein Receptor Upregulators Acting via a Novel Mechanism

  摘要：

  The synthesis and biological activity of a new series of benzamides and related compounds that upregulate the expression of the low-density lipoprotein (LDL) receptor in human hepatocytes (HepG2 cells) by a novel mechanism are described. The lead compound, N-[5-[(3-cyclohexylpropionyl)amino]-2-methylphenyl]-4-hydroxybenzamide (1, RPR102359), increased the expression of the LDL receptors in HepG2 cells by 80% when tested at a concentration of 3 mu M. Mevinolin (lovastatin) was found to increase the LDL receptor expression by 70% at the same concentration. In contrast to mevinolin, 1 was found to have no effect on cholesterol biosynthesis in liver homogenates or in HepG2 cells at doses where substantial upregulation of the LDL receptor was observed and thus stimulated LDL receptor expression by a novel mechanism.

  DOI：

  10.1021/jm960153q

文献信息

• Amide derivatives useful as inhibitors of the production of cytokines
  申请人：ASTRAZENECA AB

  公开号：US20030105142A1

  公开（公告）日：2003-06-05

  The invention concerns amide derivatives of formula (I) wherein R 3 is (1-6C)alkyl or halogeno; Q 1 is heteroaryl which is optionally substituted with 1, 2, 3, or 4 substituents such as hydroxy, halogeno, trifluoromethyl, (1-6C)alkyl, (1-6C)alkoxy, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, amino-(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, heteroaryl and heterocyclyl; p is 0-2 and R 2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q 2 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or in vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

  本发明涉及式（I）的酰胺衍生物，其中R3是（1-6C）烷基或卤素基；Q1是杂环芳基，可以用1、2、3或4个取代基，例如羟基、卤素基、三氟甲基、（1-6C）烷基、（1-6C）烷氧基、羟基-（1-6C）烷基、（1-6C）烷氧基-（1-6C）烷基、羟基-（2-6C）烷氧基、氨基-（2-6C）烷基氨基、N-（1-6C）烷基-（1-6C）烷基氨基-（2-6C）烷基氨基、芳基、杂环芳基和杂环烷基；p为0-2，R2是羟基和卤素基等取代基；q为0-4；Q2包括可选取代的芳基、环烷基、杂环芳基和杂环烷基；或其药学上可接受的盐或体内可水解的酯；其制备方法、包含它们的制药组合物以及它们在治疗细胞因子介导的疾病或医学状况中的用途。
• AMIDE DERIVATIVES USEFUL AS INHIBITORS OF THE PRODUCTION OF CYTOKINES
  申请人：AstraZeneca AB

  公开号：EP1102750A1

  公开（公告）日：2001-05-30
• US6432949B1
  申请人：——

  公开号：US6432949B1

  公开（公告）日：2002-08-13
• US7060700B2
  申请人：——

  公开号：US7060700B2

  公开（公告）日：2006-06-13
• [EN] AMIDE DERIVATIVES USEFUL AS INHIBITORS OF THE PRODUCTION OF CYTOKINES<br/>[FR] DERIVES D'AMIDES UTILES COMME INHIBITEURS DE LA PRODUCTION DE CYTOKINES
  申请人：ZENECA LTD

  公开号：WO2000007991A1

  公开（公告）日：2000-02-17

  The invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; Q1 is heteroaryl which is optionally substituted with 1, 2, 3, or 4 substituents such as hydroxy, halogeno, trifluoromethyl, (1-6C)alkyl, (1-6C)alkoxy, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, amino-(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, heteroaryl and heterocyclyl; p is 0-2 and R2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q2 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or in vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.