5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one | 129221-01-8

• 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: 5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 5-(3,5-dichlorophenyl)-3H-1,3,4-oxadiazol-2-one
• CAS: 129221-01-8
• 化学式: C₈H₄Cl₂N₂O₂
• 分子量: 231.038
• InChiKey: INUMHFZEUVWVFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one 在 盐酸 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-[(4-amino-5-chloro-2-methoxyphenyl)methyl]-5-[3,5-dichlorophenyl]-1,3,4-oxadiazol-2-(3H)-one
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n
• 作为产物：
  描述：

  3,5-二氯苯甲酸 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 24.5h， 生成 5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n

文献信息

• [EN] NEW DIAZASPIROCYCLOALKANE AND AZASPIROCYCLOALKANE<br/>[FR] NOUVEAUX COMPOSÉS DIAZASPIROCYCLOALCANE ET AZASPIROCYCLOALCANE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013186159A1

  公开（公告）日：2013-12-19

  The invention provides novel compounds having the general formula (I), wherein R1, R2, Y and W are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般公式（I）的新化合物，其中R1、R2、Y和W如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• NEW DIAZASPIROCYCLOALKANE AND AZASPIROCYCLOALKANE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150099734A1

  公开（公告）日：2015-04-09

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , Y and W are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般化学式（I）的新化合物，其中R1、R2、Y和W如本文所述，包括该化合物的组合物以及使用该化合物的方法。
• Reaction of 1,3,4-oxadiazolones with free L-<i>α</i>-amino acids: A facile synthesis of novel 3,5-disubstituted hydantoins
  作者：Yasuo Saegusa、Shigeo Harada、Shigeo Nakamura

  DOI：10.1002/jhet.5570270349

  日期：1990.3

  A series of novel 3,5-disubstituted hydantoins 3a-1 were easily synthesized in one-step from the reaction of 2-phenyl-1,3,4-oxadiazolin-5-ones 1a-h with various free L-α-amino acids 2a-e in m-cresol at 150°. An alternative route leading to the formation of 3-benzamido-5-isopropylhydantoin 3c was also developed to make clear the reaction mechanism.

  从2-苯基-1,3,4-恶二唑啉-5-酮1a-h与各种游离L- α-氨基的反应可轻松一步合成一系列新颖的3,5-二取代乙内酰脲3a-1酸2A-E在米甲酚在150℃。还开发了导致3-苯甲酰胺基-5-异丙基乙内酰脲3c形成的替代途径以阐明反应机理。
• Palladium-Catalyzed Oxidative O–H/N–H Carbonylation of Hydrazides: Access to Substituted 1,3,4-Oxadiazole-2(3<i>H</i>)-ones
  作者：Fanghua Ji、Xianwei Li、Wei Guo、Wanqing Wu、Huanfeng Jiang

  DOI：10.1021/acs.joc.5b00664

  日期：2015.6.5

  cyclocarbonylation provides an efficient and direct approach for the construction of valuable 1,3,4-oxadiazole-2(3H)-ones and their derivatives. The reaction also facilitated the convenient synthesis of BMS-191011, an opener of the cloned large-conductance Ca2+-activated potassium channel, providing an attractive method for medicinal chemistry.

  开发了一种新颖的钯催化的C–O，C–N键形成的氧化环化反应。分子内环羰基化为构建有价值的1,3,4-恶二唑-2（3 H）-ones及其衍生物提供了一种有效而直接的方法。该反应还促进了BMS-191011的便捷合成，BMS-191011是克隆的大电导Ca 2+活化的钾通道的开放剂，为药物化学提供了有吸引力的方法。
• Diazaspirocycloalkane and azaspirocycloalkane
  申请人：Hoffmann-La Roche Inc.

  公开号：US10633384B2

  公开（公告）日：2020-04-28

  Compounds having the general formula (I) wherein R1, R2, Y and W are as described herein, compositions including the compounds and methods of using the compounds as autotaxin inhibitors.

  具有通式 (I) 的化合物 其中 R1、R2、Y 和 W 如本文所述，包括这些化合物的组合物以及将这些化合物用作自体表皮生长因子抑制剂的方法。