SCP-1 | 182502-68-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: SCP-1
• 英文别名: 2-(1,1-dioxo-1,2-dihydrobenzo[d]isothiazol-3-one-2-yl)-N-(4-hydroxyphenyl)acetamide；2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)acetamide；N-(4-hydroxyphenyl)-2-(1,1,3-trioxo-1,2-benzothiazol-2-yl)acetamide；2-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)-N-(4-hydroxyphenyl)acetamide；1,2-Benzisothiazole-2(3H)-acetamide, N-(4-hydroxyphenyl)-3-oxo-, 1,1-dioxide
• CAS: 182502-68-7
• 化学式: C₁₅H₁₂N₂O₅S
• 分子量: 332.337
• InChiKey: PUPNJSIFIXXJCH-UHFFFAOYSA-N

物化性质

• 熔点：
  204-206 °C(Solv: ethanol (64-17-5))
• 密度：
  1.585±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  SCP-1 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.33h， 以80%的产率得到2-({[(4-hydroxyphenyl)carbamoyl]methyl}sulfamoyl)benzoic acid
  参考文献：
  名称：

  Analgesic compounds, their synthesis and pharmaceutical compositions containing them

  摘要：

  本发明揭示了一些新的镇痛化合物，这些化合物是通过N-酰化的4-羟基苯胺衍生物的水解制备而成，还揭示了它们的合成方法和包含它们的药物组合物。这些化合物出人意料地具有高度的镇痛活性，且对肝脏毒性影响较小，因此在慢性疼痛的治疗中比传统的非甾体抗炎药（NSAIDs）更加有用。

  公开号：

  US06806291B1
• 作为产物：
  描述：

  对氨基苯酚 在 Na⁽¹⁺⁾*HSO₄^(1-)*SiO₂ = NaHSO₄*SiO₂ 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 SCP-1
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR AMELIORATING PAIN
  [FR] COMPOSITIONS ET MÉTHODES POUR SOULAGER LA DOULEUR

  摘要：

  这项发明涉及用于治疗或缓解疼痛的组合物、方法和工具包。

  公开号：

  WO2019040122A1

文献信息

• Synthesis, hepatotoxic evaluation and antipyretic activity of nitrate ester analogs of the acetaminophen derivative SCP-1
  作者：Madhurima Das、Surjyadipta Bhattacharjee、Frank R. Fronczek、Nicolas G. Bazan、Mark L. Trudell

  DOI：10.1016/j.bmcl.2018.09.020

  日期：2018.12

  A series of nitrate ester analogues of the acetaminophen derivative SCP-1 were prepared by triflic acid catalyzed O-acylation of SCP-1 with chloroalkanoyl chlorides followed by nitration with silver nitrate. The chloroesters and corresponding nitrate esters were obtained in high yields. Preliminary hepatotoxicity studies revealed nitrate esters 5b (MD-38) and 5c (MD-39) to be well tolerated by human

  对乙酰氨基酚衍生物SCP-1的一系列硝酸酯类似物的制备是通过三氟乙酸用氯代烷酰氯对SCP-1进行O-酰化，然后用硝酸银硝化来制备的。高产率地获得了氯酯和相应的硝酸酯。初步的肝毒性研究显示，人肝细胞对硝酸酯5b（MD-38）和5c（MD-39）具有很好的耐受性，并且对所测试的三种细胞色素P450酶（CYP3A4，CYP2E1和CYP2D6）的影响很小。另外，硝酸酯5c（MD-39）表现出与对乙酰氨基酚相似的解热活性。
• Compositions and methods for ameliorating pain and reducing fever
  申请人：The Board of Supervisors of Louisiana State University and Agricultural and Mechanical College

  公开号：US11007199B2

  公开（公告）日：2021-05-18

  This invention is directed to compositions, methods and kits that can be used for the treatment or amelioration of pain and fever.

  本发明涉及可用于治疗或改善疼痛和发烧的组合物、方法和试剂盒。
• A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis
  作者：Hernan A. Bazan、Surjyadipta Bhattacharjee、Carolina Burgos、Javier Recio、Valentina Abet、Amanda R. Pahng、Bokkyoo Jun、Jessica Heap、Alexander J. Ledet、William C. Gordon、Scott Edwards、Dennis Paul、Julio Alvarez-Builla、Nicolas G. Bazan

  DOI：10.1016/j.ejmech.2020.112600

  日期：2020.9

  Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity. 1 is a non-hepatotoxic, metabolically unstable lipophilic ApAP analog that is not antipyretic. The newly synthesized 3 is a non-hepatotoxic ApAP analog that is stable, lipophilic, and retains analgesia and antipyresis. Intraperitoneal or po administration of the new chemical entities (NCEs), 3b and 3r, in concentrations equal to a toxic dose of ApAP did not result in the formation of NAPQI. Unlike livers from NCE-treated mice, the livers from ApAP-treated mice demonstrated large amounts of nitrotyrosine, a marker of mitochondrial free radical formation, and loss of hepatic tight junction integrity. Given the widespread use of ApAP, hepatotoxicity risk with overuse, and the ongoing opioid epidemic, these NCEs represent a novel, non-narcotic therapeutic pipeline. (C) 2020 The Authors. Published by Elsevier Masson SAS.
• Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs
  作者：Anthony L. Vaccarino、Dennis Paul、Pranab K. Mukherjee、Elena B. Rodríguez de Turco、Victor L. Marcheselli、Liang Xu、Mark L. Trudell、J.M. Minguez、M.P. Matía、Carlos Sunkel、Julio Alvarez-Builla、Nicolas G. Bazan

  DOI：10.1016/j.bmc.2006.07.054

  日期：2007.3

  A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic. (c) 2006 Elsevier Ltd. All rights reserved.
• First Multigram Preparation of SCP-123, A Novel Water-Soluble Analgesic
  作者：Lei Miao、Liang Xu、Kenneth W. Narducy、Mark L. Trudell

  DOI：10.1021/op900113b

  日期：2009.7.17

  A short multigram process for the preparation of the analgesic compound SCP-123 (4) and its sodium salt has been developed.