2-fluoro-4-[(4-methyl-1-piperazinyl)sulfonyl]benzenamine | 486422-39-3

• 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: 2-fluoro-4-[(4-methyl-1-piperazinyl)sulfonyl]benzenamine
• 英文别名: 2-fluoro-4-((4-methylpiperazin-1-yl)sulfonyl)aniline；2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylaniline
• CAS: 486422-39-3
• 化学式: C₁₁H₁₆FN₃O₂S
• 分子量: 273.331
• InChiKey: WASUUJBLFNYENH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-fluoro-4-[(4-methyl-1-piperazinyl)sulfonyl]benzenamine 在 盐酸 作用下， 反应 0.5h， 以75%的产率得到
  参考文献：
  名称：

  Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer’s Disease: Design, Synthesis, and Characterization of Pyrazines

  摘要：

  Glycogen synthase kinase-3 beta, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3 beta localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimer's disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and blood-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimer's disease.

  DOI：

  10.1021/jm201724m
• 作为产物：
  描述：

  3-氟-4-硝基苯磺酰氯 在 盐酸 、 铁粉 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 2-fluoro-4-[(4-methyl-1-piperazinyl)sulfonyl]benzenamine
  参考文献：
  名称：

  NVS-BPTF-1的合成及其生物活性评价

  摘要：

  BPTF（含溴结构域和 PHD 指的转录因子）是一种多结构域蛋白，在转录调控、T细胞稳态和干细胞多能性中起重要作用。作为染色质重塑复合物 hNURF（核小体重塑因子）的一部分，BPTF 表观遗传阅读器亚基对 BPTF 细胞功能尤为重要。在这里，我们报告了 NVS-BPTF-1 的合成，这是一种先前报道的高效和选择性 BPTF-溴结构域抑制剂。使用 NVS-BPTF-1 对 BPTF-溴结构域的抑制对参与抗原加工途径的选定蛋白质的影响的评估表明，仅针对 BPTF-溴结构域不足以观察到 PSMB8、PSMB9、TAP1 和 TAP2 蛋白的增加。

  DOI：

  10.1016/j.bmcl.2021.128208

文献信息

• Arylamines for the treatment of conditions associated with gsk-3
  申请人：Berg Stefan

  公开号：US20060052396A1

  公开（公告）日：2006-03-09

  The present invention relates to new compounds of formula (I) wherein Z, Y, X, P, Q, R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , A, m and n are defined as in any one of claims 1 to 3, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds for the treatment of conditions associated with glycogens synthase kinase-3 (GSK3).

  本发明涉及具有公式（I）的新化合物，其中Z、Y、X、P、Q、R、R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、A、m和n的定义如权利要求1至3中的任意一项，以及制备它们的过程和其中制备的新中间体，含有所述治疗活性化合物的制药配方以及使用所述活性化合物治疗与糖原合酶激酶-3（GSK3）相关的疾病的方法。
• BET-PROTEIN-INHIBITING DIHYDROPYRIDOPYRAZINONES
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160193206A1

  公开（公告）日：2016-07-07

  The present invention relates to BET protein-inhibitory, especially BRD4-inhibitory, dihydropyridopyrazinones of the general formula (I) in which A, X, R 1 , R 2 , R 3 , R 4 , R 4 , R 6 , R 7 and n have the meanings given in the description, to intermediates for preparation of the compounds according to the invention, to pharmaceutical compositions comprising the compounds according to the invention, and to the prophylactic and therapeutic use thereof in the case of hyperproliferative disorders, especially in the case of neoplastic disorders. This invention further relates to the use of BET protein inhibitors in viral infections, in neurodegenerative disorders, in inflammation diseases, in atherosclerotic disorders and in male fertility control.

  本发明涉及BET蛋白抑制剂，特别是BRD4抑制剂，通式（I）所示的二氢吡啶吡唑酮，其中A、X、R1、R2、R3、R4、R4、R6、R7和n在说明书中给出其含义，以及制备本发明化合物的中间体，包含本发明化合物的制药组合物，以及在高增殖性疾病，特别是恶性肿瘤疾病的预防和治疗中的预防和治疗用途。本发明还涉及在病毒感染、神经退行性疾病、炎症性疾病、动脉粥样硬化性疾病和男性生育控制中使用BET蛋白抑制剂。
• ARYLAMINES FOR THE TREATMENT OF CONDITIONS ASSOCIATED WITH GSK-3
  申请人：AstraZeneca AB

  公开号：EP1414801A1

  公开（公告）日：2004-05-06
• [EN] ARYLAMINES FOR THE TREATMENT OF CONDITIONS ASSOCIATED WITH GSK-3<br/>[FR] NOUVEAUX COMPOSES
  申请人：ASTRAZENECA AB

  公开号：WO2003004472A1

  公开（公告）日：2003-01-16

  The present invention relates to new compounds of formula (I) wherein Z, Y, X, P, Q, R, R?1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12¿, A, m and n are defined as in any one of claims 1 to 3, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds for the treatment of conditions associated with glycogens synthase kinase-3 (GSK3).
• Synthesis of NVS-BPTF-1 and evaluation of its biological activity
  作者：Léa Mélin、Cyrus Calosing、Olesya A. Kharenko、Henrik C. Hansen、Alexandre Gagnon

  DOI：10.1016/j.bmcl.2021.128208

  日期：2021.9

  pluripotency. As part of the chromatin remodeling complex hNURF (nucleosome remodeling factor), BPTF epigenetic reader subunits are particularly important for BPTF cellular function. Here we report the synthesis of NVS-BPTF-1, a previously reported highly potent and selective BPTF-bromodomain inhibitor. Evaluation of the impact of the inhibition of BPTF-bromodomain using NVS-BPTF-1 on selected proteins involved

  BPTF（含溴结构域和 PHD 指的转录因子）是一种多结构域蛋白，在转录调控、T细胞稳态和干细胞多能性中起重要作用。作为染色质重塑复合物 hNURF（核小体重塑因子）的一部分，BPTF 表观遗传阅读器亚基对 BPTF 细胞功能尤为重要。在这里，我们报告了 NVS-BPTF-1 的合成，这是一种先前报道的高效和选择性 BPTF-溴结构域抑制剂。使用 NVS-BPTF-1 对 BPTF-溴结构域的抑制对参与抗原加工途径的选定蛋白质的影响的评估表明，仅针对 BPTF-溴结构域不足以观察到 PSMB8、PSMB9、TAP1 和 TAP2 蛋白的增加。