2,4-diphenyl-4H-[1,3,4]oxadiazin-5-one | 109462-65-9

• 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: 2,4-diphenyl-4H-[1,3,4]oxadiazin-5-one
• 英文别名: 2,4-Diphenyl-4H-[1,3,4]oxadiazin-5-on；2,4-diphenyl-4H-1,3,4-oxadiazine-5(6H)-one；2,4-diphenyl-5,6-dihydro-4H-1,3,4-oxadiazin-5-one；2,4-diphenyl-1,3,4-oxadiazin-5-one
• CAS: 109462-65-9
• 化学式: C₁₅H₁₂N₂O₂
• 分子量: 252.272
• InChiKey: JGDXZSAXNNEXNE-UHFFFAOYSA-N

物化性质

• 沸点：
  369.3±25.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苯基苯并肼 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 4.0h， 生成 2,4-diphenyl-4H-[1,3,4]oxadiazin-5-one
  参考文献：
  名称：

  Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): A Novel, Noncompetitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) Receptor Antagonist

  摘要：

  Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.

  DOI：

  10.1021/jm301268u

文献信息

• HETERODIAZINONE DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP1153922A1

  公开（公告）日：2001-11-14

  The present invention provides a novel compound having an excellent 2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonistic action, particularly a therapeutic, preventing and ameliorating action useful for cerebral ischemia, cerebrospinal injuries, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, epilepsy, pain, spastic paralysis, multiple sclerosis etc. That is, the present invention provides a heterodiazinon compound represented by the following formula (I), a pharmacologically acceptable salt thereof or hydrates thereof.    Wherein A represents an oxygen atom, a sulfur atom or a group represented by the formula >NR3 (wherein R3 represents hydrogen atom or a lower alkyl group); R1 and R2 are the same as or different from each other and each represents an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aralkyl group, an optionally substituted heteroaryl alkyl group, an optionally substituted aryl alkenyl group, an optionally substituted heteroaryl alkenyl group, an optionally substituted piperidyl group, an optionally substituted piperazinyl group; a morpholinyl group, an optionally substituted lower cycloalkyl group, a tetrahydrofuranyl group, a tetrahydropyranyl group, an adamantyl group, an optionally substituted amino group or an optionally substituted amide group; and R4 and R5 are the same as or different from each other and each represents hydrogen atom, hydroxy, a halogen atom, nitrile group, nitro group, a lower alkyl group, an aryl group or a heteroaryl group,    provided that the compounds represented by the following formula (II): (wherein R11 and R12 are the same as or different from each other and each represents hydrogen atom, fluorine, chlorine, bromine, iodine, a C1-C2 fluoroalkyl group, a C1-C2 chloroalkyl group, a C1-C2 bromoalkyl group, a C1-C6 alkyl group, a C3-C6 cycloalkyl group, a C7-C9 aralkyl group, phenyl group, a C1-C6 alkoxy group, a C1-C6 alkylthio group, a C1-C6 alkylsulfinyl group, a C7-C9 aralkoxy group, phenoxy group, phenylthio group, phenylsulfonyl group, alkali metal carboxylate C2-C5 alkoxycarbonyl group or a group represented by the formula -N(R15)R16 (wherein R15 and R16 are the same as or different from each other and each represents hydrogen atom or a C1-C2 alkyl group); and R13 and R14 are the same as or different from each other and each represents a C1-4 alkylsulfonyl group, nitro group, a group represented by the formula -OCHnX3-n (wherein X represents fluorine, chlorine, bromine or iodine; and n is any of integers 1 to 3) or a group having the same meanings as the definitions of R11 and R12) are excluded.

  本发明提供了一种新型化合物，该化合物具有优异的 2-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗作用，特别是对脑缺血、脑脊髓损伤、阿尔茨海默病、帕金森病、肌萎缩性脊髓侧索硬化症、亨廷顿舞蹈症、癫痫、疼痛、痉挛性瘫痪、多发性硬化症等具有治疗、预防和改善作用。也就是说，本发明提供了由下式（I）代表的杂二嗪酮化合物、其药理学上可接受的盐或其水合物。 其中A代表氧原子、硫原子或由式>NR3代表的基团（其中R3代表氢原子或低级烷基）； R1 和 R2 彼此相同或不同，各自代表任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基、任选取代的杂芳基烷基、任选取代的芳基烯基、任选取代的杂芳基烯基、任选取代的哌啶基、任选取代的哌嗪基；吗啉基、任选取代的低级环烷基、四氢呋喃基、四氢呋喃基、金刚烷基、任选取代的氨基或任选取代的酰胺基；以及 R4 和 R5 彼此相同或不同，各自代表氢原子、羟基、卤素原子、腈基、硝基、低级烷基、芳基或杂芳基、 条件是下式（II）所代表的化合物 (其中 R11 和 R12 彼此相同或不同，且各自代表氢原子、氟、氯、溴、碘、C1-C2 氟烷基、C1-C2 氯烷基、C1-C2 溴烷基、C1-C6 烷基、C3-C6 环烷基、C7-C9 芳烷基、苯基、C1-C6 烷氧基、C1-C6 烷硫基、C1-C6 烷硫基、C7-C9 芳氧基、苯氧基、苯硫基、苯磺酰基、碱金属羧基 C2-C5 烷氧基羰基或由式 -N(R15)R16 所代表的基团（其中 R15 和 R16 彼此相同或不同，且各自代表氢原子或 C1-C2 烷基）；和 不包括 R13 和 R14 彼此相同或不同，且各自代表 C1-4 烷基磺酰基、硝基、由式 -OCHnX3-n 代表的基团（其中 X 代表氟、氯、溴或碘；n 为 1 至 3 的任一整数）或与 R11 和 R12 的定义具有相同含义的基团。
• Hoppenbrouwers, Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 325,332
  作者：Hoppenbrouwers

  DOI：——

  日期：——
• van Alphen, Recueil des Travaux Chimiques des Pays-Bas, 1928, vol. 47, p. 911
  作者：van Alphen

  DOI：——

  日期：——
• Justoni, Gazzetta Chimica Italiana, 1938, vol. 68, p. 49,56
  作者：Justoni

  DOI：——

  日期：——
• 1,3,4-OXADIAZIN-DERIVATE UND IHRE VERWENDUNG ALS SCHÄDLINGSBEKÄMPFUNGSMITTEL
  申请人：BAYER AG

  公开号：EP0891341B1

  公开（公告）日：2003-01-02