1-<<4-(benzyloxy)phenyl>(thiocarbonyl)>-2-(2-cyanoethyl)hydrazine | 149181-58-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-<<4-(benzyloxy)phenyl>(thiocarbonyl)>-2-(2-cyanoethyl)hydrazine
• 英文别名: N'-(2-cyanoethyl)-4-phenylmethoxybenzenecarbothiohydrazide
• CAS: 149181-58-8
• 化学式: C₁₇H₁₇N₃OS
• 分子量: 311.407
• InChiKey: AOLVXFOGBMKPMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  光气 、 1-<<4-(benzyloxy)phenyl>(thiocarbonyl)>-2-(2-cyanoethyl)hydrazine 以 甲苯 为溶剂， 反应 3.0h， 以62%的产率得到3-[5-(4-Benzyloxy-phenyl)-2-oxo-[1,3,4]thiadiazol-3-yl]-propionitrile
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00061a006
• 作为产物：
  描述：

  magnesium,phenylmethoxybenzene,bromide 在 盐酸 、 sodium hydroxide 、 sodium carbonate 作用下， 反应 12.0h， 生成 1-<<4-(benzyloxy)phenyl>(thiocarbonyl)>-2-(2-cyanoethyl)hydrazine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00061a006

文献信息

• 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.