1-(3-fluoro-4-nitrophenyl)-4-isopropylpiperazine | 1440136-74-2

• 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: 1-(3-fluoro-4-nitrophenyl)-4-isopropylpiperazine
• 英文别名: 1-(3-fluoro-4-nitrophenyl)-4-propan-2-ylpiperazine
• CAS: 1440136-74-2
• 化学式: C₁₃H₁₈FN₃O₂
• 分子量: 267.303
• InChiKey: QYULFJCWMAYNCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-fluoro-4-nitrophenyl)-4-isopropylpiperazine 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 N-(2-fluoro-4-(4-isopropylpiperazin-1-yl)phenyl)-4-(pyridin-2-yl)benzamide
  参考文献：
  名称：

  Towards Optimization of Arylamides As Novel, Potent, and Brain-Penetrant Antiprion Lead Compounds

  摘要：

  The prion diseases caused by PrPSc, in alternatively folded form of the cellular prion protein (PrPC), are rapidly progressive, fatal, and untreatable neurodegenerative disorders. We employed HTS ELISA assays to identify compounds that lower the level of PrPSc in prion-infected mouse neuroblastoma (ScN2a-cl3) cells and identified a series of arylamides. Structure-activity relationship (SAR) studies indicated that small amides with one aromatic or heteroaromatic ring on each side of the amide bond are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one of only a few arylamide hits with a piperazine group on its aniline moiety. The basic piperazine nitrogen can be protonated at physiologic pH, improving solubility, and therefore, we wanted to exploit this feature in our search for a drug candidate. An SAR campaign resulted in several key analogues, including a set with biaryl groups introduced on the carbonyl side for improved potency. Several of these biaryl analogues have submicromolar potency, with the most potent analogue 17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24, 26, and 27) Were able to traverse the blood-brain barrier.(BBB) and displayed excellent drug levels in the brains of mice following oral dosing. These biarylamides, may represent good starting points for further lead optimization for the identification of potential drug candidates for the treatment of priori diseases.

  DOI：

  10.1021/ml300454k
• 作为产物：
  描述：

  1-异丙基哌嗪 、 2,4-二氟硝基苯 在 六甲基磷酰三胺 、 potassium carbonate 作用下， 反应 48.0h， 以53%的产率得到1-(3-fluoro-4-nitrophenyl)-4-isopropylpiperazine
  参考文献：
  名称：

  Towards Optimization of Arylamides As Novel, Potent, and Brain-Penetrant Antiprion Lead Compounds

  摘要：

  The prion diseases caused by PrPSc, in alternatively folded form of the cellular prion protein (PrPC), are rapidly progressive, fatal, and untreatable neurodegenerative disorders. We employed HTS ELISA assays to identify compounds that lower the level of PrPSc in prion-infected mouse neuroblastoma (ScN2a-cl3) cells and identified a series of arylamides. Structure-activity relationship (SAR) studies indicated that small amides with one aromatic or heteroaromatic ring on each side of the amide bond are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one of only a few arylamide hits with a piperazine group on its aniline moiety. The basic piperazine nitrogen can be protonated at physiologic pH, improving solubility, and therefore, we wanted to exploit this feature in our search for a drug candidate. An SAR campaign resulted in several key analogues, including a set with biaryl groups introduced on the carbonyl side for improved potency. Several of these biaryl analogues have submicromolar potency, with the most potent analogue 17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24, 26, and 27) Were able to traverse the blood-brain barrier.(BBB) and displayed excellent drug levels in the brains of mice following oral dosing. These biarylamides, may represent good starting points for further lead optimization for the identification of potential drug candidates for the treatment of priori diseases.

  DOI：

  10.1021/ml300454k

文献信息

• [EN] CYCLIN-DEPENDENT KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES CYCLINE-DÉPENDANTES
  申请人：SPV THERAPEUTICS INC

  公开号：WO2020140055A1

  公开（公告）日：2020-07-02

  Described herein are compounds and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, methods of treatment, and medical uses. The compounds described herein are modulators of cyclin-dependent kinases, and are useful in the treatment or alleviation of protein kinase associated disorders, including cancer, infectious diseases, autoimmune diseases, or cardiovascular diseases.

  本文描述了化合物及其药用盐，以及它们的药物组合物，治疗方法和医疗用途。本文描述的化合物是细胞周期依赖性激酶的调节剂，并且在治疗或缓解蛋白激酶相关疾病方面具有用途，包括癌症，传染病，自身免疫疾病或心血管疾病。
• [EN] CYCLIN-DEPENDENT KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES DÉPENDANTES DES CYCLINES
  申请人：SPV THERAPEUTICS INC

  公开号：WO2020140052A1

  公开（公告）日：2020-07-02

  Described herein are compounds and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, methods of treatment, and medical uses. The compounds described herein are modulators of cyclin-dependent kinases, and are useful in the treatment or alleviation of protein kinase associated disorders, including cancer, infectious diseases, autoimmune diseases, or cardiovascular diseases.

  本文描述了化合物及其药用盐、药物组合物、治疗方法和医学用途。本文描述的化合物是细胞周期依赖性激酶的调节剂，并且在治疗或缓解蛋白激酶相关疾病方面具有用途，包括癌症、传染病、自身免疫疾病或心血管疾病。
• [EN] CYCLIN-DEPENDENT KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE CYCLINE-DÉPENDANTS
  申请人：SPV THERAPEUTICS INC

  公开号：WO2020140054A8

  公开（公告）日：2021-07-08
• CYCLIN-DEPENDENT KINASE INHIBITORS
  申请人：SPV THERAPEUTICS INC.

  公开号：US20220056037A1

  公开（公告）日：2022-02-24

  Described herein are compounds and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, methods of treatment, and medical uses. The compounds described herein are modulators of cyclin-dependent kinases, and are useful in the treatment or alleviation of protein kinase associated disorders, including cancer, infectious diseases, autoimmune diseases, or cardiovascular diseases.