N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]naphthalene-2-sulfonamide | 692746-92-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]naphthalene-2-sulfonamide
• CAS: 692746-92-2
• 化学式: C₂₂H₁₆N₄O₃S₂
• 分子量: 448.526
• InChiKey: UGODIOOKONOGOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]naphthalene-2-sulfonamide 以 乙腈 为溶剂， 反应 0.08h， 生成 N⁵-((R)-1-((carboxymethyl)amino)-3-((1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio)-1-oxopropan-2-yl)-L-glutamine
  参考文献：
  名称：

  PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS

  摘要：

  Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter.

  DOI：

  10.1021/jm5019093
• 作为产物：
  描述：

  萘-2-磺酰胺 在 sodium dithionite 、 titanium(IV) chloride tetrahydrofuran 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]naphthalene-2-sulfonamide
  参考文献：
  名称：

  作为新型蛋白酶体抑制剂的氢萘醌的发现和合成

  摘要：

  筛选工作导致鉴定出 PI-8182 ( 1 )，蛋白酶体的胰凝乳蛋白酶样 (CT-L) 活性抑制剂。化合物1含有氢萘醌药效基团，其 2 位为巯基乙酸侧链，4 位为噻吩磺酰胺。开发了一种有效的氢萘醌磺酰胺支架合成路线，并在内部合成了化合物1以确认其结构和活性（IC 50 = 3.0 ± 1.6 μM [ n = 25]）。1 的新型氢萘醌衍生物被设计、合成和评估为蛋白酶体抑制剂。超过 170 种衍生物的构效关系 (SAR) 指导合成表明需要巯基乙酸侧链，并且该侧链的羧酸基团对化合物1的 CT-L 抑制活性至关重要。此外，用四唑或三唑等羧酸等排体替代羧酸可大大提高效力。在位置 2 具有硫代四唑或硫代三唑侧链的化合物，其中噻吩被疏水芳基部分取代，是最活跃的化合物，其 CT-L 抑制比化合物1（化合物15e、15f）高 20 倍, 15 小时,图15j，IC 50值在200nM左右，化合物29，IC

  DOI：

  10.1021/jm201118h

文献信息

• Discovery and Synthesis of Hydronaphthoquinones as Novel Proteasome Inhibitors
  作者：Yiyu Ge、Aslamuzzaman Kazi、Frank Marsilio、Yunting Luo、Sanjula Jain、Wesley Brooks、Kenyon G. Daniel、Wayne C. Guida、Saïd M. Sebti、Harshani R. Lawrence

  DOI：10.1021/jm201118h

  日期：2012.3.8

  guided synthesis of more than 170 derivatives revealed that the thioglycolic acid side chain is required and the carboxylic acid group of this side chain is critical to the CT-L inhibitory activity of compound 1. Furthermore, replacement of the carboxylic acid with carboxylic acid isosteres such as tetrazole or triazole greatly improves potency. Compounds with a thio-tetrazole or thio-triazole side chain

  筛选工作导致鉴定出 PI-8182 ( 1 )，蛋白酶体的胰凝乳蛋白酶样 (CT-L) 活性抑制剂。化合物1含有氢萘醌药效基团，其 2 位为巯基乙酸侧链，4 位为噻吩磺酰胺。开发了一种有效的氢萘醌磺酰胺支架合成路线，并在内部合成了化合物1以确认其结构和活性（IC 50 = 3.0 ± 1.6 μM [ n = 25]）。1 的新型氢萘醌衍生物被设计、合成和评估为蛋白酶体抑制剂。超过 170 种衍生物的构效关系 (SAR) 指导合成表明需要巯基乙酸侧链，并且该侧链的羧酸基团对化合物1的 CT-L 抑制活性至关重要。此外，用四唑或三唑等羧酸等排体替代羧酸可大大提高效力。在位置 2 具有硫代四唑或硫代三唑侧链的化合物，其中噻吩被疏水芳基部分取代，是最活跃的化合物，其 CT-L 抑制比化合物1（化合物15e、15f）高 20 倍, 15 小时,图15j，IC 50值在200nM左右，化合物29，IC
• Methods and compositions for treatment of muscle wasting, muscle weakness, and/or cachexia
  申请人：Baylor College of Medicine

  公开号：US10676455B2

  公开（公告）日：2020-06-09

  Embodiments of the invention include methods of treating, preventing, and/or reduce the risk or severity of a condition selected from the group consisting of muscle wasting, muscle weakness, cachexia, and a combination thereof in an individual in need thereof. In some embodiments, particular small molecules are employed for treatment, prevention, and/or reduction in the risk of muscle wasting. In at least particular cases, the small molecules are inhibitors of STAT3.

  本发明的实施方案包括治疗、预防和/或降低有需要的个体发生选自肌肉萎缩、肌无力、恶病质及其组合的疾病的风险或严重程度的方法。在某些实施方案中，采用特定的小分子来治疗、预防和/或降低肌肉萎缩的风险。至少在特定情况下，小分子是 STAT3 的抑制剂。
• STAT3 INHIBITORS
  申请人：Tweardy David J.

  公开号：US20100041685A1

  公开（公告）日：2010-02-18

  Small molecule inhibitors of Stat3 and their derivatives are disclosed. Also described are methods to inhibit cell growth by use of Stat3 inhibitors, and the use of Stat3 inhibitors for the prevention and/or treatment of cancer. Further, inhibitors of Stat3 that also do not inhibit Stat1 are described as well as their derivatives. Methods of screening additional compounds for Stat3 inhibition activity and/or non-inhibition of Stat1 activity are also described herein.
• STAT3 Inhibitors
  申请人：Baylor College of Medicine

  公开号：US20140296270A1

  公开（公告）日：2014-10-02

  Small molecule inhibitors of Stat3 and their derivatives are disclosed. Also described are methods to inhibit cell growth by use of Stat3 inhibitors, and the use of Stat3 inhibitors for the prevention and/or treatment of cancer. Further, inhibitors of Stat3 that also do not inhibit Stat1 are described as well as their derivatives. Methods of screening additional compounds for Stat3 inhibition activity and/or non-inhibition of Stat1 activity are also described herein.
• METHODS AND COMPOSITIONS FOR PREVENTION OF ALLERGIC REACTION
  申请人：Baylor College of Medicine

  公开号：US20150031714A1

  公开（公告）日：2015-01-29

  Embodiments of the invention include methods of preventing and/or reducing the risk or severity of an allergic reaction in an individual. In some embodiments, particular small molecules are employed for prevention and/or reduction in the risk or severity of anaphylaxis. In at least particular cases, the small molecules are inhibitors of STAT3. In some cases, the small molecule comprises N-(1′,2-dihydroxy-1,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide.