3-[2-氧代-5-[4-(苯基甲氧基)苯基]-1,3,4-恶二唑-3-基]丙腈 | 147807-20-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-[2-氧代-5-[4-(苯基甲氧基)苯基]-1,3,4-恶二唑-3-基]丙腈
• 中文别名: 4-硝基苯基O-(2-乙酰氨基-2-脱氧吡喃葡萄糖基)-(1-2)-O-(6-O-甲基吡喃甘露糖基)-(1-6)-吡喃葡萄糖苷
• 英文名称: 5-(4-benzoxylphenyl)-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 5-(4-(Benzyloxy)phenyl)-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one；3-[2-oxo-5-(4-phenylmethoxyphenyl)-1,3,4-oxadiazol-3-yl]propanenitrile
• CAS: 147807-20-3
• 化学式: C₁₈H₁₅N₃O₃
• 分子量: 321.335
• InChiKey: RBWUKXWSNXXLOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(苄氧基)苯甲酸乙酯 在 一水合肼 作用下， 以 丙醇 、 乙醇 、 甲苯 为溶剂， 反应 99.0h， 生成 3-[2-氧代-5-[4-(苯基甲氧基)苯基]-1,3,4-恶二唑-3-基]丙腈
  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

• Modified Leptin Polypeptides and Their Uses
  申请人：Kraynov Vadim

  公开号：US20120149636A1

  公开（公告）日：2012-06-14

  Modified human leptin polypeptides and uses thereof are provided.

  提供了改良的人类瘦素多肽及其用途。
• 1,3-Dipolar Cycloaddition of Nitrile Imine with Carbon Dioxide: Access to 1,3,4-Oxadiazole-2(3<i>H</i>)-ones
  作者：Chun-Xiao Guo、Wen-Zhen Zhang、Ning Zhang、Xiao-Bing Lu

  DOI：10.1021/acs.joc.7b00963

  日期：2017.7.21

  Efficient synthesis of 1,3,4-oxadiazole-2(3H)-one was achieved by CsF/18-crown-6 mediated 1,3-dipolar cycloaddition of nitrile imine and 2.0 MPa of CO2. CsF/18-crown-6 played a key role in enhancing the reactivity of CO2 as a 1,3-dipolarophile. The practical utility of this transition-metal-free approach to 1,3,4-oxadiazole-2(3H)-one is highlighted by the convenient synthesis of a commercial herbicide

  通过CsF / 18-crown-6介导的腈亚胺的1,3-偶极环加成和2.0 MPa的CO2，可以实现1,3,4-恶二唑-2（3H）-1的高效合成。CsF / 18-crown-6在增强CO2作为1,3-偶极亲子的反应中起着关键作用。这种无过渡金属的方法对1,3,4-恶二唑-2（3H）-one的实际应用通过方便地合成市售除草剂Oxadiazon和MAO B抑制剂得到了强调。
• 一种二氧化碳合成恶草酮等1,3,4-噁二唑-2- 酮类化合物的方法
  申请人：大连理工大学

  公开号：CN106866573B

  公开（公告）日：2019-12-17

  本发明公开了一种二氧化碳合成恶草酮等1,3,4‑噁二唑‑2‑酮类化合物的方法。该方法是在高压釜中加入酰卤腙原料和溶剂，以碱和添加剂为促进剂，通入二氧化碳，在0～70摄氏度搅拌反应6～24小时，反应结束后冷却至室温，缓慢释放未反应的二氧化碳，反应液加水稀释后用乙酸乙酯萃取，浓缩得粗产品，经柱层析纯化得到1,3,4‑噁二唑‑2‑酮类化合物。本发明使用二氧化碳替代传统的光气和一氧化碳，操作安全简单，毒性低，对环境友好，反应原料和试剂简单易得，反应底物类型普适性广，后处理过程简单，目标产物收率高，有利于工业生产，在农药、医药及天然产物合成中具有广泛用途。
• CANNABINOID RECEPTOR ANTAGONISTS/INVERSE AGONISTS USEFUL FOR TREATING OBESITY
  申请人：McElroy John Francis

  公开号：US20070213302A1

  公开（公告）日：2007-09-13

  The present invention provides novel pyrazoles that are useful as cannabinoid receptor antagonists and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, and/or cardiometabolic disorders.

  本发明提供了一种新型吡唑，可作为大麻素受体拮抗剂，并提供了其药物组合物和治疗肥胖、糖尿病和/或心脏代谢紊乱的方法。
• [EN] CANNABINOID RECEPTOR ANTAGONISTS/INVERSE AGONISTS<br/>[FR] ANTAGONISTES/AGONISTES INVERSES DES RÉCEPTEURS DES CANNABINOÏDES
  申请人：JENRIN DISCOVERY INC

  公开号：WO2014018695A1

  公开（公告）日：2014-01-30

  The present invention provides novel, diastereomeric pyrazolines that are useful as cannabinoid receptor blockers and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, inflammatory disorders, cardiometabolic disorders, hepatic disorders, and/or cancers.

  本发明提供了新颖的、对映异构体的吡唑啉，其可用作大麻素受体阻滞剂及其药物组成物和使用它们治疗肥胖症、糖尿病、炎症性疾病、心代谢疾病、肝疾病和/或癌症的方法。