1-butyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxylic acid | 71575-75-2

• 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: 1-butyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxylic acid
• 英文别名: 1-butyl-4-oxo-6-phenyl-1,4-dihydronicotinic acid；1-Butyl-4-oxo-6-phenylpyridine-3-carboxylic acid
• CAS: 71575-75-2
• 化学式: C₁₆H₁₇NO₃
• 分子量: 271.316
• InChiKey: PWQPQCWFJDGKNE-UHFFFAOYSA-N

物化性质

• 熔点：
  121 °C
• 沸点：
  441.2±45.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  1-butyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxylic acid 、 盐酸金刚烷胺 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以30%的产率得到N3-(1-adamantyl)-1-butyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series

  摘要：

  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.

  DOI：

  10.1021/jm100286k
• 作为产物：
  描述：

  3-carbethoxy-6-phenyl-4-pyrone 在 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 1-butyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series

  摘要：

  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.

  DOI：

  10.1021/jm100286k

文献信息

• [EN] 1,4 DIHYDROPYRIDINE DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS DE LA 1,4-DIHYDROPYRIDINE ET LEURS UTILISATIONS
  申请人：UNIV LILLE II DROIT & SANTE

  公开号：WO2010133973A1

  公开（公告）日：2010-11-25

  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）的活性修改（增加或减少）直接或间接相关的疾病和紊乱中的用途。
• 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-Pyridon-3-carbonsäurederivate, diese enthaltende pharmazeutische Präparate und deren Herstellung sowie deren Verwendung
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0003144A2

  公开（公告）日：1979-07-25

  4-Pyridon-3-carbonsäurederivate der allgemeinen Formel worin R' C1-8-Alkyl, C3-10-Cycloalkyl, C3-10Cycloalkyl-C1-6- alkyl, C1-8-Alkoxy oder C1-6-Alkoxy-C1-6-alkyl; R2 Wasserstoff oder C1-6-Alkyl; R3 einen ggf. durch R4, R5 und/oder R6 substituierten Phenyl-, Phenäthyl- oder Styrylrest oder einen ggf. durch R7 substituierten, ein oder mehrere N-Atome enthaltenden aromatisch heterocyclischen 6-Ring, der über ein Ring-C-atom gebunden ist; R4 und R5 Halogen, Trifluormethyl, Hydroxy, C1-6-Alkoxy, C1-6-Alkylthio, C1-6-Alkyl, Amino, Acylamino, C1-6-Alkylamino, Di-C1-6-alkylamino, Nitro, einen über ein Ring-N- oder -C-atom gebundenen 5- oder 6- gliedrigen Heterocyclus oder beide Reste R4 und R5 gemeinsam C1-6-Alkylendioxy; Re C1-6-Alkoxy und R7 Halogen, Hydroxy, C1-6-Alkoxy, C1-6Alkylthio, C1-6 Alkyl, Amino, C1-6-Alkylamino oder Di-C1-6- alkylamino bedeuten, - mit der Einschränkung, dass R2 nicht Wasserstoff ist, wenn R' Methyl und gleichzeitig R3 Phenyl darstellen - und deren Salze, deren Herstellung in an sich bekannter Weise und deren Verwendung bei der Therapie und Prophylaxe von Krankheiten.

  通式为 4-吡啶酮-3-羧酸的衍生物 其中 R'为 C1-8-烷基、C3-10-环烷基、C3-10-环烷基-C1-6-烷基、C1-8-烷氧基或 C1-6-烷氧基-C1-6-烷基；R2 为氢或 C1-6-烷基； R3 是可被 R4、R5 和/或 R6 取代的苯基、苯乙基或苯乙烯基，或可被 R7 取代的苯基、苯乙基或苯乙烯基。被 R7 取代并含有一个或多个 N 原子的芳香杂环，该芳香杂环为 6 元环，通过环 C 原子键合；R4 和 R5 是卤素、三氟甲基、羟基、C1-6-烷氧基、C1-6-烷硫基、C1-6-烷基、氨基、酰氨基、C1-6-烷基氨基、二-C1-6-烷基氨基、硝基、通过环 N 原子或 C 原子键合的 5 或 6 元杂环，或 R4 和 R5 两个基共同是 C1-6 烷基二氧基； Re C1-6-烷氧基和 R7 卤素、羟基、C1-6-烷氧基、C1-6-烷硫基、C1-6 烷基、氨基、C1-6-烷基氨基或二-C1-6-烷基氨基、 - 如果 R'是甲基，R3 是苯基，则 R2 不能是氢、 以本身已知的方式制备它们，以及它们在治疗和预防疾病中的用途。
• 1,4-dihydropyridine derivatives and their uses
  申请人：Université de Lille 2 Droit et Santé

  公开号：EP2261211A1

  公开（公告）日：2010-12-15

  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）活性改变（增加或降低）直接或间接相关的疾病和失调中的用途。
• 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