3-(4-chlorophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one | 182633-13-2

• 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: 3-(4-chlorophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one
• 英文别名: 3-(4-Chlorophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one；3-(4-chlorophenyl)-4,4-dimethyl-1H-pyrazol-5-one
• CAS: 182633-13-2
• 化学式: C₁₁H₁₁ClN₂O
• 分子量: 222.674
• InChiKey: CARNAIQCQPSXFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one 在 劳森试剂 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.5h， 生成 5-(4-Chloro-phenyl)-4,4-dimethyl-2-(3-methyl-butyl)-2,4-dihydro-pyrazole-3-thione
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Miticidal 4,5-Dihydropyrazole-5-thiones

  摘要：

  A series of novel 4,5-dihydropyrazole-5-thiones (DHPs) was synthesised by treating the corresponding dihydropyrazolones with Lawesson's reagent and evaluated for miticidal activity against two-spotted spider mites (Tetranychus urticae Koch). Of these, 3-(4-chlorophenyl)-4,4-dimethyl-1-phenyl-4, 5-dihydropyrazole-5-thione, 3-(4-chlorophenyl)-4-ethyl-4-methyl-1-phenyl-4,5-dihydropyrazole-5-thione, 3-(4-chlorophenyl)-1-phenyl-4,5-dihydropyrazole-5-thione-4-spirocyclopentane and 4,4-dimethyl-1-phenyl-3-(4-trifluoromethyl-phenyl)-4,5-dihydropyrazole-5-thione were highly active (pEC(50) > 4 . 0) and were more effective than the miticide dicofol (pEC(50) = 3 . 879), which has traditionally been used for the control of phytophagous mites. Structure-activity relationship (SAR) studies were performed on each position of the pyrazole ring of DHPs. The results indicated that the unsubstituted phenyl, 4-substituted phenyl and thioxo groups on the 1-, 3- and 5-positions of DHPs respectively were required for activity. Quantitative SAR studies using physicochemical parameters of substituents and the capacity factor k' as a hydrophobicity index suggested that: (a) the activities of all types of DHPs examined were mainly dominated by hydrophobicity, (b) the bulkiness of 4-substituents of the 3-phenyl ring favoured the activity and (c) the log k' optimum for all DHPs was 1 . 675, equivalent to a log P-ow value of c. 5 . 0.

  DOI：

  10.1002/(sici)1096-9063(199610)48:2<165::aid-ps455>3.0.co;2-z
• 作为产物：
  描述：

  3-(4-aminophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one 在 盐酸 、 sodium nitrite 、 copper chloride dihydrate 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 以79 mg的产率得到3-(4-chlorophenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one
  参考文献：
  名称：

  用于SLFN12依赖性癌细胞杀伤的PDE3A调节剂的优化

  摘要：

  6-（4-（二乙氨基）-3-硝基苯基）-5-甲基-4,5-二氢哒嗪-3（2 H）-one或DNMDP有效和选择性地抑制磷酸二酯酶3A和3B（PDE3A和PDE3B）并杀死通过诱导PDE3A / B与SFLN12的相互作用来形成癌细胞。使用表型生存力分析评估了DNMDP类似物的结构-活性关系（SAR），得到了几种具有合适药代动力学特性的化合物，可用于体内分析。这些化合物之一BRD9500在癌症的SK-MEL-3异种移植模型中具有活性。

  DOI：

  10.1021/acsmedchemlett.9b00360

文献信息

• Identification of Phenylpyrazolone Dimers as a New Class of Anti‐ <i>Trypanosoma cruzi</i> Agents
  作者：Maarten Sijm、Julianna Siciliano de Araújo、Alba Ramos Llorca、Kristina Orrling、Lydia Stiny、An Matheeussen、Louis Maes、Iwan J. P. Esch、Maria Nazaré Correia Soeiro、Geert Jan Sterk、Rob Leurs

  DOI：10.1002/cmdc.201900370

  日期：2019.9.18

  library led to the identification of 2,2′‐methylenebis(5‐(4‐bromophenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied

  查加斯病正在成为一个世界性问题；目前估计超过六百万人受到感染。目前使用的两种药物，苯并硝唑和硝呋莫司，需要长期治疗方案，在慢性感染阶段疗效有限，并且已知会引起不良反应。对内部文库进行表型筛选，鉴定出 2,2'-亚甲基双(5-(4-溴苯基)-4,4-二甲基-2,4-二氢-3 H-吡唑-3-酮)，苯基二氢吡唑啉酮二聚体，其针对克氏锥虫的体外 pIC 50值为 5.4 。最初的优化是通过改变苯环的取代基来完成的，之后尝试替换苯环。最后，二聚体单元之间的连接体发生变化，最终形成 2,2'-亚甲基双(5-(3-溴-4-甲氧基苯基)-4,4-二甲基-2,4-二氢-3 H-吡唑- 3-one (NPD-0228) 是最有效的类似物。NPD-0228 对T. cruzi细胞内无鞭毛体的体外 pIC 50值为 6.4 ，对人 MRC-5 细胞系和小鼠心肌细胞没有明显毒性。
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US20160016913A1

  公开（公告）日：2016-01-21

  Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.

  本发明涉及一些化合物，例如吡啶并咪唑酮，可用于治疗癌症等疾病。
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS UTILISABLES EN VUE DU TRAITEMENT DU CANCER
  申请人：BROAD INST INC

  公开号：WO2014164704A3

  公开（公告）日：2014-12-31
• Compounds And Compositions For The Treatment Of Cancer
  申请人：The Broad Institute, Inc.

  公开号：US20180244629A1

  公开（公告）日：2018-08-30

  Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.
• US9890127B2
  申请人：——

  公开号：US9890127B2

  公开（公告）日：2018-02-13