N-benzyl-3-methyl-N-phenylisonicotinamide | 951027-30-8

• 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-benzyl-3-methyl-N-phenylisonicotinamide
• 英文别名: N-Benzyl-3-methyl-N-phenyl-isonicotinamide；N-benzyl-3-methyl-N-phenylpyridine-4-carboxamide
• CAS: 951027-30-8
• 化学式: C₂₀H₁₈N₂O
• 分子量: 302.376
• InChiKey: RHFOKBOFEKDMKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-甲基-4-甲酸嘧啶 、 苯甲基苯胺 在 吡啶 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以87%的产率得到N-benzyl-3-methyl-N-phenylisonicotinamide
  参考文献：
  名称：

  G-Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5) Agonists Reduce the Production of Proinflammatory Cytokines and Stabilize the Alternative Macrophage Phenotype

  摘要：

  GPBAR1 (also known as TGR5) is a G-protein-coupled receptor (GPCR) that triggers intracellular signals upon ligation by various bile acids. The receptor has been studied mainly for its function in energy expenditure and glucose homeostasis, and there is little information on the role of GPBAR1 in the context of inflammation. After a high-throughput screening campaign, we identified isonicotinamides exemplified by compound 3 as nonsteroidal GPBAR1 agonists. We optimized this series to potent derivatives that are active on both human and murine GPBAR1. These agonists inhibited the secretion of the proinflammatory cytokines TNF-alpha and IL-12 but not the antiinflammatory IL-10 in primary human monocytes. These effects translate in vivo, as compound 15 inhibits LPS induced TNF-alpha and IL-12 release in mice. The response was GPBAR1 dependent, as demonstrated using knockout mice. Furthermore, agonism of GPBAR1 stabilized the phenotype of the alternative, noninflammatory, M2-like type cells during differentiation of monocytes into macrophages. Overall, our results illustrate an important regulatory role for GPBAR1 agonists as controllers of inflammation.

  DOI：

  10.1021/jm501052c

文献信息

• HETEROCYCLIC AMIDES FOR USE AS PHARMACEUTICALS
  申请人：Arista Luca

  公开号：US20100261758A1

  公开（公告）日：2010-10-14

  Compounds of Formula (I) wherein R 1 is aryl, cyclohexyl or heterocyclyl, or (C 1-4 )alkyl substituted by aryl, cyclohexyl or heterocyclyl, R 2 is defined heterocyclyl, R 3 is alkyl, aryl, cyclohexyl or heterocyclyl, or (C 1-4 )alkyl substituted by aryl, cyclohexyl or heterocyclyl, R 4 is H or alkyl, or R 3 and R 4 together with the carbon atom to which they are attached are cycloalkyl fused with aryl, and their use as pharmaceuticals.

  化合物的公式（I），其中R1是芳基，环己基或杂环基，或被芳基，环己基或杂环基取代的（C1-4）烷基，R2是定义的杂环基，R3是烷基，芳基，环己基或杂环基，或被芳基，环己基或杂环基取代的（C1-4）烷基，R4是H或烷基，或R3和R4与它们所连接的碳原子一起是环状烷基与芳基融合，以及它们作为药物的用途。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• Use of dianhydrogalactitol and analogs and derivatives thereof to treat recurrent malignant glioma or progressive secondary brain tumor
  申请人：DelMar Pharmaceuticals, Inc.

  公开号：US11026914B2

  公开（公告）日：2021-06-08

  Methods and compositions suitable for the treatment of malignancies such as recurrent glioma and progressive secondary brain tumor are disclosed. These methods employ a hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, or a derivative or analog of diacetyldianhydrogalactitol. The compositions can include such hexitol derivatives.

  本发明公开了适用于治疗复发性胶质瘤和进行性继发性脑瘤等恶性肿瘤的方法和组合物。这些方法采用己糖醇衍生物，如二氢半乳糖醇、二氢半乳糖醇的衍生物或类似物、二乙酰二氢半乳糖醇或二乙酰二氢半乳糖醇的衍生物或类似物。组合物可以包括此类己糖醇衍生物。
• AMIDE DERIVATIVES AND THEIR APPLICATION FOR THE TREAMENT OF G PROTEIN RELATED DISEASES
  申请人：NOVARTIS AG

  公开号：EP2001851A2

  公开（公告）日：2008-12-17
• METHODS FOR TREATING TYROSINE-KINASE-INHIBITOR-RESISTANT MALIGNANCIES IN PATIENTS WITH GENETIC POLYMORPHISMS OR AHI1 DYSREGULATIONS OR MUTATIONS EMPLOYING DIANHYDROGALACTITOL, DIACETYLDIANHYDROGALACTITOL, DIBROMODULCITOL, OR ANALOGS OR DERIVATIVES THEREOF
  申请人：Del Mar Pharmaceuticals

  公开号：EP2872161A2

  公开（公告）日：2015-05-20