3-(1,4-thiazinan-4-ylsulfonyl)aniline | 1042777-08-1

• 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: 3-(1,4-thiazinan-4-ylsulfonyl)aniline
• 英文别名: 3-Thiomorpholin-4-ylsulfonylaniline
• CAS: 1042777-08-1
• 化学式: C₁₀H₁₄N₂O₂S₂
• mdl: MFCD11172059
• 分子量: 258.365
• InChiKey: GVSRPSKFHHKQPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(1,4-thiazinan-4-ylsulfonyl)aniline 在 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 48.5h， 生成 2-(4-fluorobenzenesulfonamido)-N-[3-(thiomorpholine-4-sulfonyl)phenyl]acetamide
  参考文献：
  名称：

  Structure–Activity Studies on Bis-Sulfonamide SHIP1 Activators

  摘要：

  含 SH2 的肌醇多磷酸 5-磷酸酶 1（SHIP1）会抑制 PI3K 的活性，因此在治疗炎症性疾病方面具有重要意义。最近的研究结果还表明，SHIP1 能促进小胶质细胞吞噬溶酶体降解脂质，这表明该酶可能是治疗阿尔茨海默病的靶点。因此，提高 SHIP1 活性的小分子药物可能会在这些领域有所裨益。最近，我们发现了一种能提高 SHIP1 酶活性的双磺酰胺。我们合成并评估了一系列类似的 SHIP1 激活剂，以确定其结构-活性关系并提高其体内稳定性。现已发现一些新的类似物，其效力有所提高。此外，母体结构中的噻吩和硫代吗啉都可以被不含低价硫原子的基团取代，这为获得不易氧化降解的激活剂提供了一种途径。

  DOI：

  10.3390/molecules28248048
• 作为产物：
  描述：

  4-(3-Nitrophenyl)sulfonylthiomorpholine 在 tin(II) chloride dihdyrate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 3-(1,4-thiazinan-4-ylsulfonyl)aniline
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors

  摘要：

  Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-alpha and IL-6 production. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.031

文献信息

• Design and synthesis of leucylaniline derivatives as leucyl-tRNA synthetase inhibitors
  作者：Jinghan Luo、Chengjun Wu、Yanjun Hu、Xingxing Jia、Yu Chen、Tiemin Sun

  DOI：10.1039/d1nj04543a

  日期：——

  By simulating the structure of Leu-AMP, an intermediate of tRNA synthesis, 26 leu-arylamine derivatives were designed and synthesized by retaining leucine and replacing adenosine phosphate with amido-substituted aniline. All compounds were designed under the guidance of computer aided drug design, and their drug-like properties were fully considered. The inhibitory activities of all compounds against

  通过模拟tRNA合成中间体Leu-AMP的结构，设计合成了26个leu-arylamine衍生物，保留亮氨酸，用氨基取代的苯胺代替磷酸腺苷。所有化合物均在计算机辅助药物设计指导下进行设计，并充分考虑了其类药性质。测试了所有化合物对 LeuRS 抑制酶和草分枝杆菌 1180的抑制活性。大多数化合物显示出对 LeuRS 抑制酶和草分枝杆菌 1180的抑制活性。六种化合物（18、19、20、21、24和25 _ _ _ _ _ _) 使用结核分枝杆菌 H37Ra进行筛选。这些化合物对结核分枝杆菌H37Ra有很强的抑制作用。分子对接研究也显示出同样的结果，充分验证了设计思路。我们还发现化合物上氢键受体的存在导致与蛋白质的关键氨基酸形成强氢键。
• PYRAZOLE-AMIDES FOR USE IN THE TREATMENT OF PAIN
  申请人：Icagen, Inc.

  公开号：EP1451160B1

  公开（公告）日：2010-01-13
• Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors
  作者：Charlotte Chaulet、Cécile Croix、David Alagille、Sylvain Normand、Adriana Delwail、Laure Favot、Jean-Claude Lecron、Marie-Claude Viaud-Massuard

  DOI：10.1016/j.bmcl.2010.12.031

  日期：2011.2

  Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-alpha and IL-6 production. (C) 2010 Elsevier Ltd. All rights reserved.
• Structure–Activity Studies on Bis-Sulfonamide SHIP1 Activators
  作者：Shea T. Meyer、Sandra Fernandes、Robert E. Anderson、Angela Pacherille、Bonnie Toms、William G. Kerr、John D. Chisholm

  DOI：10.3390/molecules28248048

  日期：——

  The SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) enzyme opposes the activity of PI3K and therefore is of interest in the treatment of inflammatory disorders. Recent results also indicate that SHIP1 promotes phagolysosomal degradation of lipids by microglia, suggesting that the enzyme may be a target for the treatment of Alzheimer’s disease. Therefore, small molecules that increase SHIP1 activity may have benefits in these areas. Recently we discovered a bis-sulfonamide that increases the enzymatic activity of SHIP1. A series of similar SHIP1 activators have been synthesized and evaluated to determine structure–activity relationships and improve in vivo stability. Some new analogs have now been found with improved potency. In addition, both the thiophene and the thiomorpholine in the parent structure can be replaced by groups without a low valent sulfur atom, which provides a way to access activators that are less prone to oxidative degradation.

  含 SH2 的肌醇多磷酸 5-磷酸酶 1（SHIP1）会抑制 PI3K 的活性，因此在治疗炎症性疾病方面具有重要意义。最近的研究结果还表明，SHIP1 能促进小胶质细胞吞噬溶酶体降解脂质，这表明该酶可能是治疗阿尔茨海默病的靶点。因此，提高 SHIP1 活性的小分子药物可能会在这些领域有所裨益。最近，我们发现了一种能提高 SHIP1 酶活性的双磺酰胺。我们合成并评估了一系列类似的 SHIP1 激活剂，以确定其结构-活性关系并提高其体内稳定性。现已发现一些新的类似物，其效力有所提高。此外，母体结构中的噻吩和硫代吗啉都可以被不含低价硫原子的基团取代，这为获得不易氧化降解的激活剂提供了一种途径。