5-(4-benzyloxyphenyl)-1,3,4-oxadiazol-2(3H)-one | 147807-38-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-benzyloxyphenyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 5-(4-phenylmethoxyphenyl)-3H-1,3,4-oxadiazol-2-one
• CAS: 147807-38-3
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: AJSSRNKFDNKLQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-benzyloxyphenyl)-1,3,4-oxadiazol-2(3H)-one 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 52.0h， 生成 4-butyl-5-(4-benzyloxyphenyl)-2H-1,2,4-triazole-3(4H)-one
  参考文献：
  名称：

  Synthesis and Anticonvulsant Activity Evaluation of 4-butyl-5-(4- alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones

  摘要：

  设计并合成了一系列4-丁基-5-(4-烷氧基苯基)-2H-1,2,4-三唑-3(4H)-酮(6a-6u)，并通过最大电击试验和旋转体试验评估了这些化合物的抗惊厥作用和神经毒性。在合成的化合物中，4-丁基-5-(4-(2-氟苄基)苯基)-2H-1,2,4-三唑-3 (4H)-酮（6k）的药效最强，ED50 值为 27.4 mg/kg，保护指数（PI = TD50/ED50）值为 12.0。除了抗 MES 的药效外，化合物 6k 对戊烯四唑（PTZ）、3-巯基丙酸（3-MP）和双谷氨酸（BIC）诱导的癫痫发作也有很强的抑制作用，这表明其抗惊厥活性可能涉及包括增强 GABA 能活性在内的作用机制。

  DOI：

  10.2174/1570180810666131122003939
• 作为产物：
  描述：

  过氧化氢酶 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 15.5h， 生成 5-(4-benzyloxyphenyl)-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  Synthesis and Anticonvulsant Activity Evaluation of 4-butyl-5-(4- alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones

  摘要：

  设计并合成了一系列4-丁基-5-(4-烷氧基苯基)-2H-1,2,4-三唑-3(4H)-酮(6a-6u)，并通过最大电击试验和旋转体试验评估了这些化合物的抗惊厥作用和神经毒性。在合成的化合物中，4-丁基-5-(4-(2-氟苄基)苯基)-2H-1,2,4-三唑-3 (4H)-酮（6k）的药效最强，ED50 值为 27.4 mg/kg，保护指数（PI = TD50/ED50）值为 12.0。除了抗 MES 的药效外，化合物 6k 对戊烯四唑（PTZ）、3-巯基丙酸（3-MP）和双谷氨酸（BIC）诱导的癫痫发作也有很强的抑制作用，这表明其抗惊厥活性可能涉及包括增强 GABA 能活性在内的作用机制。

  DOI：

  10.2174/1570180810666131122003939

文献信息

• 1,3,4-oxadiazol-2(3H)-one derivatives, their preparation and their
  申请人：Synthelabo

  公开号：US05525619A1

  公开（公告）日：1996-06-11

  1,3,4-Oxadiazol-2(3H)-one derivatives, of formula ##STR1## in which R.sub.1 represents either a hydrogen atom or a linear or branched (C.sub.1-4)alkyl group which is substituted with a hydroxyl group, a phenoxy group, a (C.sub.1-4)alkoxy group, a (C.sub.1-4)alkylthio group, a mercapto group, a (C.sub.1-4)alkoxy-(C.sub.1-4)alkoxy group, a di(C.sub.1-4)alkylamino group or an N-(C.sub.1-4)alkyl-N-propynylamino group, or represents a (C.sub.3-4)alkynyl group, and R.sub.2 either represents a linear or branched (C.sub.1-8)alkyl group which is substituted with one or more halogen atoms and/or a hydroxyl group, a 1-imidazolyl group or a 3-tetrahydropyranyl group, or represents a trifluoro(C.sub.3-5)alkenyl group, in the form of pure enantiomers or mixtures of enantiomers, including racemic mixtures, as well as the addition salts thereof with pharmaceutically acceptable acids, are useful as inhibitors of monoamine oxidase B.

  公式为##STR1##的1,3,4-噁二唑-2（3H）-酮衍生物，其中R.sub.1表示氢原子或线性或支链（C.sub.1-4）烷基，该烷基被羟基，苯氧基，（C.sub.1-4）烷氧基，（C.sub.1-4）烷基硫基，巯基，（C.sub.1-4）烷氧基 -（C.sub.1-4）烷氧基，二（C.sub.1-4）烷基氨基或N-（C.sub.1-4）烷基-N-丙炔基氨基取代，或表示（C.sub.3-4）炔基；R.sub.2表示线性或支链（C.sub.1-8）烷基，该烷基被一种或多种卤素原子和/或羟基，1-咪唑基或3-四氢吡喃基取代，或表示三氟（C.sub.3-5）烯基，以纯对映体或对映体混合物的形式存在，包括外加药物可接受酸盐，作为单胺氧化酶B的抑制剂。
• Dérivés de 1,3,4-oxadiazol-2(3H)-one, leur préparation et leur application comme inhibiteurs de monoamine oxydase
  申请人：SYNTHELABO

  公开号：EP0655445A1

  公开（公告）日：1995-05-31

  L'invention concerne des dérivés de 1,3,4-oxadiazol-2(3H)one, de formule générale (I) dans laquelle R₁ représente soit un atome d'hydrogène, soit un groupe (C₁₋₄)alkyle linéaire ou ramifié, substitué par un groupe hydroxy, phénoxy, (C₁₋₄)alcoxy, (C₁₋₄)alkylthio, mercapto, (C₁₋₄)alcoxy-(C₁₋₄)alcoxy, di(C₁₋₄)alkylamino ou N-(C₁₋₄)alkyl-N-propynylamino, soit un groupe (C₃₋₄)alcynyle, et R₂ représente soit un groupe (C₁₋₈)alkyle linéaire ou ramifié, substitué par un ou plusieurs atomes d'halogène et/ou un groupe hydroxy, 1-imidazolyle ou 3-tétrahydropyranyle, soit un groupe trifluoro(C₃₋₅)alcényle, sous forme d'énantiomères purs ou de mélanges d'énantiomères, y compris de mélanges racémiques, ainsi que leurs sels d'addition aux acides pharmaceutiquement acceptables. Application en comme inhibiteurs de monoamine oxydase, en particulier MAO-B.

  本发明涉及通式 (I) 的 1,3,4-恶二唑-2(3H)-1 衍生物 其中 R₁ 代表氢原子或被羟基、苯氧基、(C₁₋₄)烷氧基取代的直链或支链(C₁₋₄)烷基、(C₁₋₄)烷硫基、巯基、(C₁₋₄)烷氧基-(C₁₋₄)烷氧基、二(C₁₋₄)烷基氨基或 N-(C₁₋₄)烷基-N-丙炔基氨基，或 (C₃₋₄)炔基，且 R₂ 代表被一个或多个卤素原子和/或羟基、1-咪唑基或 3-四氢吡喃基取代的直链或支链 (C₁₋₈)烷基，或三氟(C₃₋₅)烯基、 纯对映异构体或对映异构体混合物，包括外消旋混合物，以及它们与药学上可接受的酸的加成盐。用作单胺氧化酶抑制剂，特别是 MAO-B。
• 5-[4-(Benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives and related analogs: new reversible, highly potent, and selective monoamine oxidase type B inhibitors
  作者：Fathi Mazouz、Salah Gueddari、Claude Burstein、Daniel Mansuy、Rene Milcent

  DOI：10.1021/jm00061a006

  日期：1993.4

  Thirty-three new 5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives including related analogues, designed as inhibitors of monoamine oxidase type B (MAO B), were synthesized and investigated both in vitro and ex vivo for their abilities to inhibit selectively rat brain MAO B over MAO A. Three inhibitors were found to act as reversible, highly potent, and selective MAO B inhibitors, namely the nitrile derivative 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (12a) and two closely related homologues, the corresponding oxadiazolethione 13a and the alcohol 14b. Their IC50(MAO B) values are in the low nanomolar range of 1.4-4.6 nM and their selectivities, estimated by the ratio of IC50 values (A/B), are from 3200 to >71 400. Compound 12a exhibited the highest activity against MAO B. Its IC50 was evaluated to be 1.4 nM with a quasitotal selectivity (>71 400) toward this enzyme. In ex vivo studies, 12a showed a reversible and short duration of action. MAO B was markedly inhibited with the oral dose of 1 mg/kg without any alteration of MAO A, and the inhibition almost did not exceed 24 h. Its ED50 (1 h after oral administration) was evaluated to be 0.56 mg (1.7 mumol)/kg. Remarkably, MAO A was not affected at doses as high as 1500 mg/kg, po. In addition, no apparent toxicity or behavioral anomaly was observed during the treatment even at the maximum administrated dose. SAR studies emphasize the existence of three binding sites to the enzyme with a special importance of the terminal phenyl. Analysis of the inhibition kinetics indicated that 12a acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO B with a K(i) value of 0.22 muM and an overall K(i)* value at equilibrium of 0.7 nM.
• US5525619A
  申请人：——

  公开号：US5525619A

  公开（公告）日：1996-06-11
• Synthesis and Anticonvulsant Activity Evaluation of 4-butyl-5-(4- alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones
  作者：Zi-Shi Zhu、Shi-Ben Wang、Xian-Qing Deng、Da-Chuan Liu、Zhe-Shan Quan

  DOI：10.2174/1570180810666131122003939

  日期：2014.4.2

  A series of 4-butyl-5-(4-alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones (6a-6u) was designed and synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test. Among the synthetic compounds, 4-butyl-5-(4-(2-fluorinebenzyl)phenyl)-2H-1,2,4-triazole-3 (4H)-one (6k) was the most potent with ED50 value of 27.4 mg/kg and protective index (PI = TD50/ED50) value of 12.0. Besides the anti-MES efficacy, the potency of compound 6k against seizures induced by pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3- MP), and bicuculline (BIC) was also established, which suggested that the mechanisms of action including enhancing of GABAergic activity might be involved in its anticonvulsant activity.

  设计并合成了一系列4-丁基-5-(4-烷氧基苯基)-2H-1,2,4-三唑-3(4H)-酮(6a-6u)，并通过最大电击试验和旋转体试验评估了这些化合物的抗惊厥作用和神经毒性。在合成的化合物中，4-丁基-5-(4-(2-氟苄基)苯基)-2H-1,2,4-三唑-3 (4H)-酮（6k）的药效最强，ED50 值为 27.4 mg/kg，保护指数（PI = TD50/ED50）值为 12.0。除了抗 MES 的药效外，化合物 6k 对戊烯四唑（PTZ）、3-巯基丙酸（3-MP）和双谷氨酸（BIC）诱导的癫痫发作也有很强的抑制作用，这表明其抗惊厥活性可能涉及包括增强 GABA 能活性在内的作用机制。