2-Chloro-1-[4-(2,4-difluorophenyl)piperazin-1-yl]ethanone | 1055347-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-Chloro-1-[4-(2,4-difluorophenyl)piperazin-1-yl]ethanone
• CAS: 1055347-40-4
• 化学式: C₁₂H₁₃ClF₂N₂O
• 分子量: 274.698
• InChiKey: VBSRUXSODOKNIA-UHFFFAOYSA-N

物化性质

• 沸点：
  409.4±45.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-吡啶甲醇 、 2-Chloro-1-[4-(2,4-difluorophenyl)piperazin-1-yl]ethanone 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 生成 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone
  参考文献：
  名称：

  4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators

  摘要：

  Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.036
• 作为产物：
  描述：

  氯乙酰氯 、 1-(2,4-二氟苯基)哌嗪 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-Chloro-1-[4-(2,4-difluorophenyl)piperazin-1-yl]ethanone
  参考文献：
  名称：

  4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators

  摘要：

  Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.036

文献信息

• A 2B adenosine receptor antagonists: Design, synthesis and biological evaluation of novel xanthine derivatives
  作者：Sujay Basu、Dinesh A. Barawkar、Vidya Ramdas、Yogesh Waman、Meena Patel、Anil Panmand、Santosh Kumar、Sachin Thorat、Rajesh Bonagiri、Dilip Jadhav、Partha Mukhopadhyay、Vandna Prasad、B. Srinivasa Reddy、Arnab Goswami、Sandhya Chaturvedi、Suraj Menon、Azfar Quraishi、Indraneel Ghosh、Sushant Dusange、Shalini Paliwal、Abhay Kulkarni、Vikas Karande、Rhishikesh Thakre、Gaurav Bedse、Sreekanth Rouduri、Jayasagar Gundu、Venkata P. Palle、Anita Chugh、Kasim A. Mookhtiar

  DOI：10.1016/j.ejmech.2016.11.007

  日期：2017.2

  affinity adenosine receptor that functions by Gs mediated elevation of cAMP and subsequent downstream signaling. The receptor has been implicated in lung inflammatory disorders like COPD and asthma. Several potent and selective A2BAdoR antagonists have been reported in literature, however most of the compounds suffer from poor pharmacokinetic profile. Therefore, with the aim to identify novel, potent and

  甲2BA Dor是低亲和力腺苷受体，通过GS功能介导的cAMP的升高和随后的下游信号传导。该受体与肺炎性疾病如COPD和哮喘有关。在文献中已经报道了几种有效的和选择性的A 2B AdoR拮抗剂，但是大多数化合物的药代动力学特性较差。因此，为了鉴定具有改善的药代动力学特性的新颖，有效和选择性的A 2B AdoR拮抗剂，我们首先探索了更受约束的MRS-1754形式（4）。为了改善代谢稳定性，尝试了几种接头修饰，以取代黄嘌呤头基的C8位和末端苯环之间的酰胺接头以及不同的苯基或其他杂芳基。SAR优化导致鉴定了两种新型A 2B AdoR拮抗剂，即8- 1- [5-Oxo-1-（4-三氟甲基-苯基）-吡咯烷-3-基甲基] -1H-吡唑-4-基} -1 ，3-二丙基-黄嘌呤（31）和8-（1- 2-氧代-2- [4-（3-三氟甲基-苯基）-哌嗪-1-基]-乙基} -1H-吡唑-4-基）-1,3-二丙
• 4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators
  作者：Hui Xiong、Todd A. Brugel、Michael Balestra、Dean G. Brown、Kelly A. Brush、Caprice Hightower、Lindsay Hinkley、Valerie Hoesch、James Kang、Gerard M. Koether、John P. McCauley、Francis M. McLaren、Laura M. Panko、Thomas R. Simpson、Reed W. Smith、James M. Woods、Becky Brockel、Vijay Chhajlani、Reto A. Gadient、Nathan Spear、Linda A. Sygowski、Minli Zhang、Jalaj Arora、Nathalie Breysse、Julie M. Wilson、Methvin Isaac、Abdelmalik Slassi、Megan M. King

  DOI：10.1016/j.bmcl.2010.10.036

  日期：2010.12

  Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models. (C) 2010 Elsevier Ltd. All rights reserved.