1-[(4-nitrobenzene)sulfonyl]-4-phenylpiperazine | 346691-54-1

• 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-[(4-nitrobenzene)sulfonyl]-4-phenylpiperazine
• 英文别名: 1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine；1-(4-nitrophenyl)sulfonyl-4-phenylpiperazine
• CAS: 346691-54-1
• 化学式: C₁₆H₁₇N₃O₄S
• mdl: MFCD00495570
• 分子量: 347.395
• InChiKey: XODLTOYHPDBTRW-UHFFFAOYSA-N

物化性质

• 沸点：
  543.3±60.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[(4-nitrobenzene)sulfonyl]-4-phenylpiperazine 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 20.0h， 生成 N-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]acrylamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

  摘要：

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.

  DOI：

  10.1021/jm201310y
• 作为产物：
  描述：

  N-苯基哌嗪 、 对硝基苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-[(4-nitrobenzene)sulfonyl]-4-phenylpiperazine
  参考文献：
  名称：

  苯磺酰胺衍生物作为有效TRPV4抑制剂治疗急性肺损伤的探索及构效关系研究

  摘要：

  RN-9893 是 Renovis Inc. 鉴定的一种 TRPV4 拮抗剂，表现出对 TRPV4 通道的显着抑制作用。这项研究涉及合成和评估三个系列的 RN-9893 类似物的 TRPV4 抑制功效。值得注意的是，与 RN-9893 (IC = 2.07 ± 0.90 μM) 相比，化合物和对 TRPV4 的抑制效力增加了 2.9 至 4.5 倍 (IC = 0.71 ± 0.21 μM 和 0.46 ± 0.08 μM)。两种化合物的 TRPV4 当前抑制率也显着优于 RN-9893（10 μM 时为 87.6 % 和 83.2 %，而 RN-9893 为 49.4 %）。首次在小鼠模型中对这些 RN-9893 类似物进行了分析，腹腔注射 10 mg/kg 或 10 mg/kg 可显着减轻脂多糖 (LPS) 诱导的急性肺损伤症状。这些结果表明化合物和化合物是治疗急性肺损伤的有希望的候选者。

  DOI：

  10.1016/j.bioorg.2024.107396

文献信息

• [EN] NOVEL POTASSIUM CHANNEL BLOCKER<br/>[FR] NOUVEAU BLOQUANT DU CANAL POTASSIQUE
  申请人：XENTION LTD

  公开号：WO2010023445A1

  公开（公告）日：2010-03-04

  The present invention provides a compound of formula (I):or its salts or pharmaceutically acceptable derivatives wherein; R1 is selected from the group consisting of optionally substituted arylalkyl, optionally substituted aryl, optionally substituted heteroarylalkyl and optionally substituted heteroaryl; R2 is selected from the group consisting of optionally substituted acyl, optionally substituted sulfonyl and optionally substituted sulfamoyl; R3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino carbonyl, optionally substituted amino sulfonyl or nitrile; X1 is selected from a group consisting of a chemical bond, CR7R8, C(=O), C(=NH), NR9, NHC(O), and SO2 wherein; R7 and R8 are independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl or; R7 and R8 together form an optionally substituted C4-6 cycloalkyl ring; R9 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aryl and optionally substituted heteroaryl; A represents an optionally substituted saturated or partially saturated 4-7 membered ring with the general formula (A): or is selected from formula (B): For each occurrence; X2 is CH or N; X3 is CH2, CH(R5a), C(R5a)(R5b), NH, N(R5c), O or S; X4 is independently selected from C(=O), CH2, CH(R4a) or C(R4a)(R4b); R4a and R4b for each occurrence is independently halogen, optionally substituted amino, hydroxyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R5a and R5b for each occurrence is independently, halogen, optionally substituted amino, hydroxyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted alkanoyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R5c is optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; n = 1 or 2. The compounds are useful as potassium ion channel inhibitors.

  本发明提供了一种化合物，其化学式为(I)：或其盐或药学上可接受的衍生物，其中；R1选自可选择地取代的芳基烷基，可选择地取代的芳基，可选择地取代的杂芳基烷基和可选择地取代的杂芳基；R2选自可选择地取代的酰基，可选择地取代的磺酰基和可选择地取代的磺胺基；R3选自氢、卤素、羟基、烷氧基、芳氧基、可选择地取代的烷基、可选择地取代的氨基、可选择地取代的氨基羰基、可选择地取代的氨基磺酰基或腈的群；X1选自化学键、CR7R8、C(=O)、C(=NH)、NR9、NHC(O)和SO2的群，其中；R7和R8各自选自氢、可选择地取代的烷基、可选择地取代的环烷基、可选择地取代的芳基和可选择地取代的杂芳基或；R7和R8一起形成一个可选择地取代的C4-6环烷基环；R9选自氢、可选择地取代的烷基、可选择地取代的芳基和可选择地取代的杂芳基；A代表一个可选择地取代的饱和或部分饱和的4-7成员环，其一般式为(A)：或选自式(B)：对于每次出现；X2为CH或N；X3为CH2、CH(R5a)、C(R5a)(R5b)、NH、N(R5c)、O或S；X4独立地选自C(=O)、CH2、CH(R4a)或C(R4a)(R4b)；R4a和R4b每次出现时独立地为卤素、可选择地取代的氨基、羟基、可选择地取代的烷氧基、可选择地取代的芳氧基、可选择地取代的烷基、可选择地取代的环烷基、可选择地取代的芳基烷基、可选择地取代的芳基或可选择地取代的杂芳基；R5a和R5b每次出现时独立地为卤素、可选择地取代的氨基、羟基、可选择地取代的烷氧基、可选择地取代的芳氧基、可选择地取代的烷基、可选择地取代的烷酰基、可选择地取代的环烷基、可选择地取代的芳基烷基、可选择地取代的芳基或可选择地取代的杂芳基；R5c为可选择地取代的酰基、可选择地取代的烷基、可选择地取代的环烷基、可选择地取代的芳基烷基、可选择地取代的芳基或可选择地取代的杂芳基；n = 1或2。这些化合物可用作钾离子通道抑制剂。
• [EN] RADIOMITIGATING COMPOUNDS, COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] COMPOSÉS RADIO-ATTÉNUANTS, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV CALIFORNIA

  公开号：WO2017156222A1

  公开（公告）日：2017-09-14

  The present disclosure relates to compounds of Formula (I), compositions containing the compounds (alone or in combination with other agents), and their use to prevent, mitigate or treat damage induced by ionizing radiation.

  本公开涉及公式（I）的化合物，含有该化合物的组合物（单独或与其他药物联合使用），以及它们用于预防、缓解或治疗由电离辐射引起的损伤的用途。
• Classes of Drugs that Mitigate Radiation Syndromes
  作者：Ewa D. Micewicz、Robert D. Damoiseaux、Gang Deng、Adrian Gomez、Keisuke S. Iwamoto、Michael E. Jung、Christine Nguyen、Andrew J. Norris、Josephine A. Ratikan、Piotr Ruchala、James W. Sayre、Dörthe Schaue、Julian P. Whitelegge、William H. McBride

  DOI：10.3389/fphar.2021.666776

  日期：——

  We previously reported several vignettes on types and classes of drugs able to mitigate acute and, in at least one case, late radiation syndromes in mice. Most of these had emerged from high throughput screening (HTS) of bioactive and chemical drug libraries using ionizing radiation-induced lymphocytic apoptosis as a readout. Here we report the full analysis of the HTS screen of libraries with 85,000 small molecule chemicals that identified 220 “hits.” Most of these hits could be allocated by maximal common substructure analysis to one of 11 clusters each containing at least three active compounds. Further screening validated 23 compounds as being most active; 15 of these were cherry-picked based on drug availability and tested for their ability to mitigate acute hematopoietic radiation syndrome (H-ARS) in mice. Of these, five bore a 4-nitrophenylsulfonamide motif while 4 had a quinoline scaffold. All but two of the 15 significantly (p &lt; 0.05) mitigated H-ARS in mice. We had previously reported that the lead 4-(nitrophenylsulfonyl)-4-phenylpiperazine compound (NPSP512), was active in mitigating multiple acute and late radiation syndromes in mice of more than one sex and strain. Unfortunately, the formulation of this drug had to be changed for regulatory reasons and we report here on the synthesis and testing of active analogs of NPSP512 (QS1 and 52A1) that have increased solubility in water and in vivo bioavailability while retaining mitigator activity against H-ARS (p &lt; 0.0001) and other radiation syndromes. The lead quinoline 057 was also active in multiple murine models of radiation damage. Taken together, HTS of a total of 150,000 bioactive or chemical substances, combined with maximal common substructure analysis has resulted in the discovery of diverse groups of compounds that can mitigate H-ARS and at least some of which can mitigate multiple radiation syndromes when given starting 24 h after exposure. We discuss what is known about how these agents might work, and the importance of formulation and bioavailability.

  我们之前曾经报道过几个案例，关于能够缓解小鼠急性和至少一个晚期辐射综合征的药物类型和类别。其中大多数是通过高通量筛选（HTS）生物活性和化学药物库，利用电离辐射诱导的淋巴细胞凋亡作为读数来发现的。在这里，我们报告了对拥有85,000种小分子化学物质的库进行HTS筛选的完整分析，共鉴定出220个“命中”。其中大多数的命中能够通过最大公共子结构分析分配到11个簇中，每个簇至少包含三个活性化合物。进一步的筛选验证了23个化合物最为活跃；其中15个基于药物可用性进行挑选，并测试其在小鼠中缓解急性造血放射综合征（H-ARS）的能力。其中5个具有4-硝基苯磺酰胺基团，而4个具有喹啉结构。其中除了两个化合物外，其余15个化合物在小鼠中明显（p &lt; 0.05）缓解了H-ARS。我们之前曾经报道过，领先的4-（硝基苯磺酰基）-4-苯基哌嗪化合物（NPSP512），在缓解多种小鼠急性和晚期辐射综合征方面具有活性，适用于多个性别和品系的小鼠。不幸的是，由于监管原因，这种药物的配方不得不改变，我们在这里报告了NPSP512的活性类似物（QS1和52A1）的合成和测试，这些类似物在水中具有更高的溶解度和in vivo生物利用度，同时保留了对H-ARS（p &lt; 0.0001）和其他辐射综合征的缓解作用。领先的喹啉057化合物也在多个小鼠辐射损伤模型中表现出活性。总之，对共计150,000种生物活性或化学物质进行HTS，结合最大公共子结构分析，已经发现了能够缓解H-ARS的各种化合物群体，其中至少有一些能够在暴露后24小时开始给予缓解多种辐射综合征。我们讨论了这些药物如何发挥作用的已知情况，以及配方和生物利用度的重要性。
• Novel Potassium Channel Blockers
  申请人：JOHN Derek Edward

  公开号：US20100087437A1

  公开（公告）日：2010-04-08

  The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives wherein R 1 , R 2 , R 3 , X 1 , and A are defined herein. The compounds are useful as potassium ion channel inhibitors.

  本发明提供公式(I)化合物或其盐或药学上可接受的衍生物，其中R1、R2、R3、X1和A的定义如本文所述。该化合物可作为钾离子通道抑制剂。
• Method of treating fibrosis
  申请人：BCN Biosciences L.L.C.

  公开号：US11229635B2

  公开（公告）日：2022-01-25

  The present disclosure is directed to method of treatment for treating or ameliorating various conditions pertaining such as bone marrow recovery (or blood cell production), fibrosis, inflammatory diseases, inhibition of cancer cell growth, propagation or malignancy, thrombocytopenia, wound healing, and conditions related to stem cells by the administration of BCN057, 512, or an analog thereof.

  本公开涉及通过施用BCN057、512或其类似物治疗或改善各种相关病症的方法，如骨髓恢复（或血细胞生成）、纤维化、炎症性疾病、抑制癌细胞生长、繁殖或恶性肿瘤、血小板减少、伤口愈合以及与干细胞相关的病症。