5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one | 72116-06-4

• 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-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 5-(3,4-dichlorophenyl)-3H-1,3,4-oxadiazol-2-one
• CAS: 72116-06-4
• 化学式: C₈H₄Cl₂N₂O₂
• 分子量: 231.038
• InChiKey: UOMZJZLXDZFENX-UHFFFAOYSA-N

物化性质

• 熔点：
  193-195 °C(Solv: benzene (71-43-2))
• 密度：
  1.69±0.1 g/cm3(Predicted)

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-(3,4-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-[3,4-dichlorophenyl]-1,3,4-oxadiazol-2-(3H)-one hydrochloride
  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：

  3,4-二氯苯甲酸 在 硫酸 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 20.0h， 生成 5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  5-(3,4-二氯苯基)-1,3,4-恶二唑-2(3H)-one的一些新型曼尼希碱及其抗炎活性

  摘要：

  非甾体抗炎药 (NSAID) 广泛用于治疗风湿性关节炎、疼痛和许多不同类型的炎症性疾病，会引起严重的胃肠道 (GI) 副作用。存在于其化学结构上的游离羧酸基团与所有常规 NSAID 相关的 GI 毒性相关。用 1,3,4-恶二唑生物电子等排体替换该官能团是获得无胃肠道副作用的抗炎剂的常用策略。在目前的工作中，合成了一组新的 5-(3,4-二氯苯基)-1,3,4-恶二唑-2(3H)-one Mannich 碱，并基于 IR、1H NMR 和元素分析结果。首先测试目标化合物的细胞毒性，以确定用于抗炎筛选的无毒浓度。通过体外脂多糖 (LPS) 诱导的 NO 产生和体内角叉菜胶足垫水肿与溃疡形成来评估化合物的抗炎作用。在 LPS 诱导的 RAW 264.7 巨噬细胞中，大多数化合物对亚硝酸盐的产生显示出抑制活性，而化合物 5a、5h 和 5j 通过抑制 NO 的产生而表现出最好的特性。为了评估化合

  DOI：

  10.1002/ardp.201700153

文献信息

• Synthesis and antimalarial effects of<i>N,N</i>-dialkyl-6-(substituted phenyl)-1,2,4,5-tetrazin-3-amines
  作者：Leslie M. Werbel、Dennis J. Mcnamara、Norman L. Colbry、Judith L. Johnson、Margaret J. Degnan、Barbara Whitney

  DOI：10.1002/jhet.5570160511

  日期：1979.7

  3-(methylthio)-6-(substituted phenyl)-1,2,4,5-tetrazines (VII) were obtained by thiobenzoylation of hydrazinecarbohydrazonothioic acid methyl ester with [[(substituted phenyl)thioxomethyl]thio]-acetic acids (V) to afford the 1,2-dihydro-3-(methylthio)-6-(substituted phenyl)-1,2,4,5-tetrazines (VI). Oxidation with bromine in acetic acid provided the desired intermediates. The target 6-(substituted phenyl)-1

  一系列N，N的合成描述了通过两种途径的-二烷基-6-（取代的苯基）-1，2，4，5-四嗪-3-胺（IV）。第一种途径（方案I）涉及甲for（II）到3-溴-6-（取代的苯基）-1，2，4，5-四嗪（III）的氧化环化，然后用胺处理。第二种（方案II）利用胺处理3-（甲硫基）-6-（取代的苯基）-1，2，4，5-四嗪（VII）以提供所需的产物。中间体3-（甲硫基）-6-（取代的苯基）-1,2,4,5-四嗪（VII）是通过肼碳酰肼基硫代甲酸甲酯与[[（（取代的苯基）硫代羰基甲基]硫代]-乙酸的硫代苯甲酰化而制得的（V）得到1，2-二氢-3-（甲硫基）-6-（取代的苯基）-1，2，4，5-四嗪（VI）。在乙酸中用溴氧化可提供所需的中间体。目标6-（取代的苯基）-1,2,4，
• Diphenyl oxadiazolones as potassium channel modulators
  申请人：Bristol-Myers Squibb Company

  公开号：US05869509A1

  公开（公告）日：1999-02-09

  Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein "Het" is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol- 2-yl, and pyridinyl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

  化合物1的新型化合物可用于治疗对大导电性钙激活钾通道开放剂反应的疾病：其中"Het"是一组特定的杂环基团之一；Z独立地为每次出现选择O或S；R.sup.a，R.sup.b和R.sup.c各自独立地选择氢，卤素，OH，CF.sub.3，provided R.sup.c不是氢；当R.sup.a和R.sup.b为氢时，R.sup.c可以是从咪唑-1-yl，morpholinomethyl，N-甲基咪唑-2-yl和吡啶基中选择的杂环基团之一；R.sup.d和R.sup.e各自独立地选择氢，卤素，CF.sub.3，NO.sub.2或咪唑-1-yl；m，n和p各自独立地选择O或1的整数；而R.sup.f和R.sup.g各自独立地选择氢；C.sub.1-4烷基；或R.sup.f和R.sup.g与它们所连接的氮原子一起选择从N-甲基哌嗪，morpholine，thiomorpholine，N-苄基哌嗪和咪唑啉酮中选择的杂环基团之一。
• 5-Phenyl-1,3,4-oxadiazol-2(3<i>H</i>)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit
  作者：William Mahy、Nicky J. Willis、Yuguang Zhao、Hannah L. Woodward、Fredrik Svensson、James Sipthorp、Luca Vecchia、Reinis R. Ruza、James Hillier、Svend Kjær、Sarah Frew、Amy Monaghan、Magda Bictash、Patricia C. Salinas、Paul Whiting、Jean-Paul Vincent、E. Yvonne Jones、Paul V. Fish

  DOI：10.1021/acs.jmedchem.0c01391

  日期：2020.11.12

  Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with druglike chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.
• 5-(3,4-dichlorophenyl)-3-{[4-(2-pyridyl)piperazine-1-yl]methyl}-1,3,4-oxadiazole-2(3H)-one: Synthesis, characterization, X-ray and DFT structures
  作者：Z. S. Şahin、İ. Özkan、M. Köksal、Ş. Işık

  DOI：10.1134/s0022476612050162

  日期：2012.9

  5-(3,4-Dichlorophenyl)-3-[4-(2-pyridyl)piperazine-1-yl)]methyl}-1,3,4-oxadiazole-2(3H)-one C18H17Cl2N5O2 (3) is synthesized and characterized by IR, H-1 NMR, C-13 NMR, elemental analyses, single-crystal X-ray diffraction, and the molecular structure is also optimized at the B3LYP/6-31G(d,p) level using density functional theory (DFT). All data obtained from the spectral studies support the structural properties of 3. The molecules are linked principally by C-HaEuro broken vertical bar O hydrogen bonds involving carbonyl atoms and carboxylate O atoms, forming R (2) (2) (16) and R (4) (2) (20) rings that link to give a one-dimensional network of molecules. An extensive two-dimensional network of C-HaEuro broken vertical bar O hydrogen bonds and pi aEuro broken vertical bar pi interactions are responsible for crystal stabilization.
• WERBEL L. M.; MCNAMARA D. J.; COLBRY N. L.; JOHNSON J. L.; DEGNAN M. J.; +, J. HETEROCYCL. CHEM., 1979, 16, NO 5, 881-894
  作者：WERBEL L. M.、 MCNAMARA D. J.、 COLBRY N. L.、 JOHNSON J. L.、 DEGNAN M. J.、 +

  DOI：——

  日期：——