6-methyl-4-oxo-1-pentyl-1,4-dihydropyridine-3-carboxylic acid | 1256382-85-0

• 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-methyl-4-oxo-1-pentyl-1,4-dihydropyridine-3-carboxylic acid
• 英文别名: 6-methyl-4-oxo-1-pentylpyridine-3-carboxylic acid
• CAS: 1256382-85-0
• 化学式: C₁₂H₁₇NO₃
• 分子量: 223.272
• InChiKey: JWXXZRGLAFTBIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methyl-4-oxo-1-pentyl-1,4-dihydropyridine-3-carboxylic acid 在 potassium phosphate 、 palladium diacetate 、 一氯化碘 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 calcium carbonate 、 三环己基膦 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 41.0h， 生成 N3-(1-adamantyl)-6-methyl-4-oxo-1-pentyl-5-phenyl-1,4-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands Part 2: Discovery of New Agonists Endowed with Protective Effect Against Experimental Colitis

  摘要：

  Further on to our earlier work on the 4-oxo-1,4-dihydropyridine, we describe herein our strategy to get access to potent selective CB2 receptor agonists. Thus, we designed and synthesized 29 compounds, evaluated on both hCB(1) and hCB(2) cannabinoid receptors, and assessed 11 of them in the TNBS-induced colitis model in mice. Compound 48 was found to be the most efficient of our series, exhibiting an exquisite protection against experimental colitis, superior to the one observed after treatment with Pentasa.

  DOI：

  10.1021/jm3008568
• 作为产物：
  描述：

  3-(dimethylaminomethylene)-6-methylpyran-2,4-dione 、 1-氨基戊烷 在 potassium tert-butylate 、 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以73%的产率得到6-methyl-4-oxo-1-pentyl-1,4-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  [EN] 1,4 DIHYDROPYRIDINE DERIVATIVES AND THEIR USES
  [FR] DÉRIVÉS DE LA 1,4-DIHYDROPYRIDINE ET LEURS UTILISATIONS

  摘要：

  本发明涉及式(I)的1,4-二氢吡啶衍生物及其在治疗和/或预防与大麻素受体2（CB2）的活性修改（增加或减少）直接或间接相关的疾病和紊乱中的用途。

  公开号：

  WO2010133973A1

文献信息

• 1,4-Dihydropyridine Derivatives and Their Uses
  申请人：Millet Regis

  公开号：US20120149735A1

  公开（公告）日：2012-06-14

  The present invention relates to 1,4-dihydropyridine derivatives of the formula (I) and their uses in the treatment and/or prevention of diseases and disorders directly or indirectly associated with the modification (increase or decrease) of the activity of the cannabinoid receptor 2 (CB2).

  本发明涉及式（I）的1,4-二氢吡啶衍生物及其在治疗和/或预防与大麻素受体2（CB2）的活性调节（增加或减少）直接或间接相关的疾病和障碍方面的用途。
• 4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series
  作者：Jamal El Bakali、Giulio G. Muccioli、Nicolas Renault、Delphine Pradal、Mathilde Body-Malapel、Madjid Djouina、Laurie Hamtiaux、Virginie Andrzejak、Pierre Desreumaux、Philippe Chavatte、Didier M. Lambert、Régis Millet

  DOI：10.1021/jm100286k

  日期：2010.11.25

  Growing evidence shows that CB2 receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective CB2 agonists, we describe here the medicinal chemistry approach leading to the development of CB2 receptor inverse agonists with a 4-oxo-1,4-dihydropyridine scaffold. The compounds reported here show high affinity and potency at the CB2, receptor while showing only modest affinity for the centrally expressed CB1 cannabinoid receptor. Further, we found that the functionality of this series is controlled by its C-6 substituent because agonists bear a methyl or a tert-butyl group and inverse agonists, a phenyl or 4-chlorophenyl group, respectively. Finally, in silico studies suggest that the C-6 substituent could modulate the conformation of W6.48 known to be critical in GPCR activation.
• Synthesis of Bioorganometallic Nanomolar-Potent CB₂ Agonists Containing a Ferrocene Unit
  作者：Supojjanee Sansook、Wei Tuo、Lucas Lemaire、Aurélien Tourteau、Amélie Barczyk、Xavier Dezitter、Frédérique Klupsch、Natascha Leleu-Chavain、Graham J. Tizzard、Simon J. Coles、Régis Millet、John Spencer

  DOI：10.1021/acs.organomet.6b00575

  日期：2016.10.10
• 1,4 DIHYDROPYRIDINE DERIVATIVES AND THEIR USES
  申请人：Université de Lille 2 Droit et Santé

  公开号：EP2432763A1

  公开（公告）日：2012-03-28