5-(3-methoxyphenyl)-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1,6-naphthyridin-2(1H)-one | 219846-31-8

• 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: 5-(3-methoxyphenyl)-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1,6-naphthyridin-2(1H)-one
• 英文别名: AC-3933；Radequinil；3-(5-methyl-1,2,4-oxadiazol-3-yl)-5-(3-methoxyphenyl)-1,6-naphthyridin-2(1H)-one；5-(3-methoxyphenyl)-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-1,6-naphthyridin-2-one
• CAS: 219846-31-8
• 化学式: C₁₈H₁₄N₄O₃
• 分子量: 334.334
• InChiKey: JQOFKKWHXGQABB-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：10 mg/mL（29.91 mM；超声加热并加热至 60°C）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

生物活性

Radequinil（AC-3933）是一种苯二氮卓类受体(BzR)的部分反向激动剂。它与GABA(-)和GABA(+)配体结合的Ki值分别为5.15 nM和6.11 nM。

靶点

Ki值：5.15±0.39 nM（GABA(-)配体），6.11±0.26 nM（GABA(+)配体）

反应信息

• 作为产物：
  描述：

  1,2-dihydro-5-(3-methoxyphenyl)-2-oxo-1,6-naphthyridin-3-amidoxime 以 水 为溶剂， 生成 5-(3-methoxyphenyl)-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  US6172079

  摘要：

  公开号：

文献信息

• Intermediates for 5-substituted-3-oxadiazolyl-1,6-Naphthyridin-2(1H)-one derivatives
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US06277993B1

  公开（公告）日：2001-08-21

  A 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivative of the formula (I): wherein Het is oxadiazolyl, R1 is H, lower alkyl, cyclo-lower alkyl, trifluoromethyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkoxy-lower alkyl, hydroxy-lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, and R2 is H, lower alkyl, cyclo-lower alkyl, cyclo-lower alkylmethyl, lower alkenyl, cyclo-lower alkenyl, lower alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted hetero-aromatic group, or a pharmaceutically acceptable acid addition salt thereof, which has high selective affinity to benzodiazepine receptor and is useful particularly as a benzodiazepine inverse agonist, for example, as psychoanaleptic drug or a drug for the treatment of dysmnesia in senile dementia or Alzheimer's disease.

  公式（I）中的5-取代-3-噻二唑基-1,6-萘啶-2（1H）-酮衍生物，其中Het是噻二唑基，R1是H，低烷基，环-低烷基，三氟甲基，低烯基，低炔基，低烷氧基，低烷氧基-低烷基，羟基-低烷基，取代或未取代芳基或取代或未取代杂芳基，R2是H，低烷基，环-低烷基，环-低烷基甲基，低烯基，环-低烯基，低炔基，取代或未取代芳基或取代或未取代杂芳基，或其药学上可接受的酸盐，具有高选择性亲和力的苯二氮平受体，特别是作为苯二氮平反向激动剂，例如，作为精神兴奋药或治疗老年痴呆或阿尔茨海默病的药物。
• NEUROGENESIS BY MUSCARINIC RECEPTOR MODULATION
  申请人：Barlow Carrolee

  公开号：US20070049576A1

  公开（公告）日：2007-03-01

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on muscarinic receptor modulation, such as via inhibition of acetylcholine esterase (AChE) activity, alone or in combination with another neurogenic agent to stimulate or activate the formation of new nerve cells.

  该即时披露描述了通过刺激或增加神经发生来治疗中枢神经系统和外周神经系统的疾病和病症的方法。该披露包括基于毒蕈碱受体调节的组合物和方法，例如通过抑制乙酰胆碱酯酶（AChE）活性，单独或与另一种神经生成剂结合以刺激或激活新神经细胞的形成。
• 5-SUBSTITUTED-3-OXADIAZOLYL-1,6-NAPHTHYRIDIN-2(1H)-ONE DERIVATIVES
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP1010699A1

  公开（公告）日：2000-06-21

  A 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivative of the formula (I): wherein Het is oxadiazolyl, R1 is H, lower alkyl, cyclo-lower alkyl, trifluoromethyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkoxy-lower alkyl, hydroxy-lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, and R2 is H, lower alkyl, cyclo-lower alkyl, cyclo-lower alkylmethyl, lower alkenyl, cyclo-lower alkenyl, lower alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group, or a pharmaceutically acceptable acid addition salt thereof, which has high selective affinity to benzodiazepine receptor and is useful particularly as a benzodiazepine inverse agonist, for example, as psychoanaleptic drug or a drug for the treatment of dysmnesia in senile dementia or Alzheimer's disease.

  式(I)的 5-取代-3-噁二唑基-1,6-萘啶-2(1H)-酮衍生物： 其中 Het 为噁二唑基，R1 为 H、低级烷基、环低级烷基、三氟甲基、低级烯基、低级炔基、低级烷氧基、低级烷氧基低级烷基、羟基低级烷基、取代或未取代的芳基、或取代或未取代的杂芳基，R2 为 H、低级烷基、环低级烷基、环低级烷甲基、低级烯基、环低级烯基、低级炔基、取代或未取代的芳基、或取代或未取代的杂芳基、或取代或未取代的杂芳香族基团，或其药学上可接受的酸加成盐，对苯二氮卓受体具有高选择性亲和力，尤其可用作苯二氮卓反向激动剂，例如，用作精神药物或治疗老年痴呆症或阿尔茨海默氏症中失忆症的药物。
• MEDICINES FOR THE PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP1295883A1

  公开（公告）日：2003-03-26

  Medicines for the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease and schizophrenia of mammals (including human beings) through the retardation or inhibition of neurodegeneration due to hypofunction of glutamic acid receptor and which contain as an active ingredient 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivatives of the formula (I): wherein Het is oxadiazolyl; R1 is hydrogen, lower alkyl, cyclo-lower alkyl, lower alkenyl, lower alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, etc.; and R2 is hydrogen, lower alkyl, cyclo-lower alkyl, substituted or unsubstituted aryl, etc., or physiologically acceptable acid addition salts thereof.

  通过延缓或抑制谷氨酸受体功能低下导致的神经退行性疾病，预防和治疗哺乳动物（包括人类）的神经退行性疾病，如阿尔茨海默病和精神分裂症的药物，其活性成分为式（I）的 5-取代-3-噁二唑基-1,6-萘啶-2(1H)-酮衍生物： 其中 Het 为噁二唑基；R1 为氢、低级烷基、环低级烷基、低级烯基、低级烷氧基、取代或未取代的芳基、取代或未取代的杂芳基等；R2 为氢、低级烷基、环低级烷基、取代或未取代的芳基等，或其生理上可接受的酸加成盐。
• MEDICINE COMPRISING COMBINATION OF ACETYLCHOLINE ESTERASE INHIBITOR AND 5-SUBSTITUTED 3-OXADIAZOLYL-1,6-NAPHTHYRIDIN-2(1H)-ONE DERIVATIVE
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP1736155A1

  公开（公告）日：2006-12-27

  The invention provides a medicine comprising a combination of an acetylcholinesterase inhibitor and a 5-substituted-3-oxadiazolyl-1,6-naphthyridin-2(1H)-one derivative of the formula (I): wherein Het is oxadiazolyl; R1 is hydrogen atom, lower alkyl, lower cycloalkyl, lower alkenyl, lower alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, etc., and R2 is hydrogen atom, lower alkyl, a lower cycloalkyl, substituted or unsubstituted aryl, etc., which is useful for treating neuropsychiatric disease-accompanying dysmnesia and other cognitive impairment; a method for treating the above-mentioned diseases; and use thereof.

  本发明提供了一种由乙酰胆碱酯酶抑制剂和5-取代-3-噁二唑基-1,6-萘啶-2(1H)-酮衍生物组合而成的药物，其式(I)为： 其中Het为噁二唑基；R1为氢原子、低级烷基、低级环烷基、低级烯基、低级烷氧基、取代或未取代的芳基、取代或未取代的杂芳基等；R2为氢原子、低级烷基、低级环烷基、取代或未取代的芳基等、 和 R2 是氢原子、低级烷基、低级环烷基、取代或未取代的芳基等，可用于治疗伴有失忆症和其他认知障碍的神经精神疾病；治疗上述疾病的方法；及其用途。