4-((4-methylpiperidin-1-yl)sulfonyl)aniline | 321970-52-9

• 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: 4-((4-methylpiperidin-1-yl)sulfonyl)aniline
• 英文别名: 4-Methyl-1-(4-nitrophenyl)sulfonylpiperidine
• CAS: 321970-52-9
• 化学式: C₁₂H₁₆N₂O₄S
• mdl: MFCD00705166
• 分子量: 284.336
• InChiKey: KMPYGZSGASXYPW-UHFFFAOYSA-N

物化性质

• 溶解度：
  3.2 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  91.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((4-methylpiperidin-1-yl)sulfonyl)aniline 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.2h， 生成 4-methyl-1-{4-[3-(4-chloro-3-(trifluoromethyl)phenyl)urea]phenyl}sulfonylpiperidine
  参考文献：
  名称：

  Design, synthesis and in vitro antitumor evaluation of novel diaryl urea derivatives bearing sulfonamide moiety

  摘要：

  一系列具有磺酰胺基团的二芳基脲衍生物被设计和合成。通过标准的MTT法筛选和评估它们对人癌细胞系MX-1、A375、HepG2、Ketr3和HT-29的体外抗肿瘤作用，以索拉非尼作为阳性对照。一些化合物显示出相较于索拉非尼对多条细胞系显著的抑制活性。特别是2,6-二甲基-4-{6-[3-(4-氯-3-(三氟甲基)苯基)脲]萘-2-基}磺酰吗啉（10d）在A375、HepG2和Ketr3中的效能最强，其IC50值为0.65–0.97 μmol/L，效力是索拉非尼的5–20倍。化合物10d成为进一步优化的有价值的先导化合物。

  DOI：

  10.1007/s11426-013-4903-z
• 作为产物：
  描述：

  3-甲基-1,5-戊二醇 在 4-二甲氨基吡啶 、 叠氮金刚烷 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 4-((4-methylpiperidin-1-yl)sulfonyl)aniline
  参考文献：
  名称：

  1-叠氮金刚烷氧化还原缩合反应制备对硝基苯磺酰胺和烷基双(二苯基亚膦)含氮环状化合物的新方法

  摘要：

  建立了一种以对硝基苯磺酰胺、双亚膦酸盐和1-叠氮基金刚烷为原料制备含氮环状化合物的新方法，该方法收率良好，且...

  DOI：

  10.1246/cl.2005.1644

文献信息

• Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
  作者：Darren W. Engers、Patrick R. Gentry、Richard Williams、Julie D. Bolinger、C. David Weaver、Usha N. Menon、P. Jeffrey Conn、Craig W. Lindsley、Colleen M. Niswender、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2010.07.007

  日期：2010.9

  Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu4 positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu4 PAM reported to date.

  在此，我们公开了一系列 4-(苯基氨磺酰基)苯基乙酰胺化合物作为 mGlu 4正变构调节剂 (PAM)的合成和 SAR，这些化合物通过功能性 HTS 鉴定。对这些化合物的迭代平行方法最终发现了 VU0364439 ( 11 )，它代表了迄今为止报道的最有效 (19.8 nM) mGlu 4 PAM。
• Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors
  作者：Bo Yang、Yanni Quan、Wuli Zhao、Yingjie Ji、Xiaotang Yang、Jianrui Li、Yi Li、Xiujun Liu、Ying Wang、Yanping Li

  DOI：10.1080/14756366.2023.2169282

  日期：2023.12.31

  Abstract To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory

   抽象的 为了探索 CDK 抑制剂在胰腺导管腺癌 (PDAC) 治疗中的潜在用途，设计、合成了一系列新型 2-((4-氨磺酰基苯基)氨基)-吡咯并[2,3-d]嘧啶衍生物，并对其进行了研究抑制 CDK 激酶活性和胰腺癌细胞增殖。大多数新型磺酰胺衍生物在细胞培养中表现出较强的CDK9抑制活性和明显的抗增殖活性。此外，两种新化合物抑制了多种人类胰腺癌细胞系的细胞增殖。最有效的化合物2g通过阻断 Rb 磷酸化来抑制癌细胞增殖，并通过下调 MIA PaCa-2 细胞中的 CDK9 下游蛋白 Mcl-1 和 c-Myc 来诱导细胞凋亡。 CDK9敲低实验表明其抗增殖活性主要由CDK9介导。此外， 2g在 AsPC-1 衍生的异种移植小鼠模型中显示出中等的肿瘤抑制作用。总而言之，这项研究为进一步优化开发潜在的 CDK 抑制剂候选物用于单独或联合使用 PDAC 治疗提供了一个新的起点。
• Exploration and structure–activity relationship research of benzenesulfonamide derivatives as potent TRPV4 inhibitors for treating acute lung injury
  作者：Mengyuan Wang、Yuehao Zhang、Xu Cai、Shangze Yang、Shiyang Sun、Sheng Zhou、Weizhen Lv、Na Du、Yan Li、Chao Ma、Kexin Ren、Mingliang Liu、Bowen Tang、Apeng Wang、Xingjuan Chen、Pengyun Li、Kai Lv、Zhibing Zheng

  DOI：10.1016/j.bioorg.2024.107396

  日期：2024.4

  RN-9893 in TRPV4 current inhibition rates (87.6 % and 83.2 % at 10 μM, against RN-9893′s 49.4 %). For the first time, these RN-9893 analogues were profiled in an mouse model, where intraperitoneal injections of or at 10 mg/kg notably mitigated symptoms of acute lung injury induced by lipopolysaccharide (LPS). These outcomes indicate that compounds and are promising candidates for acute lung injury treatment

  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。
• Potent Non-Nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase Complex
  作者：Aiming Sun、Jeong-Joong Yoon、Yan Yin、Andrew Prussia、Yutao Yang、Jaeki Min、Richard K. Plemper、James P. Snyder

  DOI：10.1021/jm701239a

  日期：2008.7

  Measles virus (MV) is one of the most infectious pathogens known. In spite of the existence of a vaccine, approximately 350000 deaths/year result from MV or associated complications. Antimeasles compounds Could conceivably diminish these statistics and provide a therapy that complements vaccine treatment. We recently described a high-throughput screening hit compound 1 (16677) against MV-infected cells with the capacity to eliminate viral reproduction at 250 nM by inhibiting the action of the virus's RNA-dependent RNA polymerase complex (RdRp). The compound, 1-methyl-3-(trifluoroi-nethyl)-N-[4-sulfonylphenyl]-1H-pyrazole-5-carboxamide, 1 carries a critical CF3 moiety on the 1,2-pyrazole ring. Elaborating on the preliminary structure-activity (SAR) study, the present work presents the synthesis and SAR of a much broader range of low nanomolar nonpeptidic MV inhibitors and speculates on the role of the CF3 functionality.
• Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response
  作者：Daniel P. Flaherty、Justin R. Miller、Danielle M. Garshott、Michael Hedrick、Palak Gosalia、Yujie Li、Monika Milewski、Eliot Sugarman、Stefan Vasile、Sumeet Salaniwal、Ying Su、Layton H. Smith、Thomas D. Y. Chung、Anthony B. Pinkerton、Jeffrey Aubé、Michael U. Callaghan、Jennifer E. Golden、Andrew M. Fribley、Randal J. Kaufman

  DOI：10.1021/ml5003234

  日期：2014.12.11

  Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the undesired proteins; however, if overwhelmed, cells trigger apoptosis by upregulating transcription factors such as C/EBP-homologous protein (CHOP). A high throughput screen was performed directed at identifying compounds that selectively upregulate the apoptotic CHOP pathway while avoiding adaptive signaling cascades, resulting in a sulfonamidebenzamide chemotype that was optimized. These efforts produced a potent and selective CHOP inducer (AC(50) = 0.8 mu M; XBP1 > 80 mu M), which was efficacious in both mouse embryonic fibroblast cells and a human oral squamous cell cancer cell line, and demonstrated antiproliferative effects for multiple cancer cell lines in the NCI-60 panel.