甲磺酰胺,N-[6-[(2,4-二氟苯基)硫代]-2,3-二氢-1-羰基-1H-茚-5-基]- | 158205-05-1

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 甲磺酰胺,N-[6-[(2,4-二氟苯基)硫代]-2,3-二氢-1-羰基-1H-茚-5-基]-
• 英文名称: 5-methanesulfonamido-6-(2,4-difluorophenylthio)-1-indanone
• 英文别名: N-[6-[(2,4-difluorophenyl)thio]-2,3-dihydro-1-oxo-1H-inden-5-yl]-methanesulfonamide；L-745-337；N-[6-(2,4-difluorophenylthio)-1-oxoindan-5-yl]methanesulphonamide；L-745,337；N-[6-[(2,4-difluorophenyl) thio]-2,3-dihydro-1-oxo-1H-inden-5-yl]methanesulfonamide；Thioflosulide；N-[6-(2,4-difluorophenyl)sulfanyl-1-oxo-2,3-dihydroinden-5-yl]methanesulfonamide
• CAS: 158205-05-1
• 化学式: C₁₆H₁₃F₂NO₃S₂
• 分子量: 369.413
• InChiKey: HDUWKQUHMUSICC-UHFFFAOYSA-N

物化性质

• 沸点：
  495.8±55.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 储存条件：
  -20°C，密封保存，并保持干燥。

制备方法与用途

生物活性

Thioflosulide (L-745337) 是一种选择性的 COX2 抑制剂，其 IC50 值为 2.3 nM，具有抗炎作用。

靶点

COX-2: 2.3 nM (IC50)

体内研究

在术后疼痛大鼠模型中，Thioflosulide (L-745337) (40-80 μg, 脊髓内注射) 与脊髓内吗啡 (0.5 nmol) 共同给药可剂量依赖性地增加痛阈值。将80 μg Thioflosulide (L-745337) 加到1 nmol 吗啡中，产生的抗痛作用大于两倍剂量的吗啡。Thioflosulide (L-745337) (0-30 mg/kg, 皮下注射) 结合脊髓内吗啡与单独使用吗啡产生相同的抗痛反应。Thioflosulide (L-745337) 在关节炎大鼠中表现出抗炎活性，其有效剂量为 0.4 mg/kg，最大抗炎剂量为 5 mg/kg。

反应信息

• 作为反应物：
  描述：

  甲磺酰胺,N-[6-[(2,4-二氟苯基)硫代]-2,3-二氢-1-羰基-1H-茚-5-基]- 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[6-(2,4-Difluoro-benzenesulfonyl)-1-oxo-indan-5-yl]-methanesulfonamide
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives

  摘要：

  The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing nonsteroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)thio]-5-methanesulfonamido-1-indanone (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted B-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t(1/2) in squirrel monkeys, and seems less ulcergenic than 2 in rats.

  DOI：

  10.1021/jm00025a007
• 作为产物：
  描述：

  5-nitro-6-bromo-1-indanone 在 盐酸 、 氢氧化钾 、 1,2-双(三甲基硅氧基)乙烷 、 potassium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 反应 47.0h， 生成 甲磺酰胺,N-[6-[(2,4-二氟苯基)硫代]-2,3-二氢-1-羰基-1H-茚-5-基]-
  参考文献：
  名称：

  Synthesis of 5-Methanesulfonamido-6-(2,4-Difluorophenylthio)-1-Indanone

  摘要：

  The ethylene ketal of 5-nitro-6-bromo-1-indanone 6 was prepared via oxidation of N-(6-Bromo-5-indanyl)-acetamide 1. A subsequent mild displace; merit and elaboration to 6-thiosubstituted-5amino indanone derivative 10 is also described.

  DOI：

  10.1080/00397919508011826

文献信息

• Combination therapy for the treatment of cancer
  申请人：Pharmacia Corporation

  公开号：US20030216410A1

  公开（公告）日：2003-11-20

  The present invention relates to methods for treatment or prevention of neoplasia disorders using protein tyrosine kinase inhibitors in combination with cyclooxygenase inhibitors, in particular cyclooxygenase-2 selective inhibitors.

  本发明涉及使用蛋白酪氨酸激酶抑制剂与环氧合酶抑制剂，特别是环氧合酶-2选择性抑制剂，联合治疗或预防肿瘤性疾病的方法。
• Antiangiogenic combination therapy for the treatment of cancer
  申请人：——

  公开号：US20020103141A1

  公开（公告）日：2002-08-01

  The present invention provides combinations of a DNA topoisomerase I inhibiting agent and a selective COX-2 inhibiting agent for preventing, treating, and/or reducing the risk of developing a neoplasia disorder in a mammal.

  本发明提供了一种DNA拓扑异构酶I抑制剂和选择性COX-2抑制剂的组合物，用于预防、治疗和/或减少哺乳动物发生肿瘤性疾病的风险。
• 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
  申请人：Merck Frosst Canada Inc.

  公开号：US05604260A1

  公开（公告）日：1997-02-18

  The Compound of Formula I and pharmaceutically acceptable salts thereof in the treatment of cyclooxygenase-2 mediated diseases are disclosed.

  公式I的化合物及其药用盐在治疗环氧合酶-2介导的疾病中被披露。
• [EN] CANNABINOID ACID ESTER COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSITIONS D'ESTER D'ACIDE CANNABINOÏDE ET LEURS UTILISATIONS
  申请人：EPM GROUP INC

  公开号：WO2020186010A1

  公开（公告）日：2020-09-17

  The present disclosure provides pharmaceutical compositions including a cannabinoid acid ester compound alone or in combination with one or more additional cannabinoid compounds. In some embodiments, the cannabinoid acid ester compound is a cannabidiolic acid ester. A variety of therapeutic applications in which the cannabinoid acid ester compounds and pharmaceutical compositions find use are also provided, including combination therapies using cannabinoid acid ester compounds and one or more additional therapeutic agents.

  本公开提供了包括大麻酸酯化合物在内或与一个或多个额外的大麻化合物结合的药物组合物。在一些实施例中，大麻酸酯化合物是大麻二酚酸酯。还提供了大麻酸酯化合物和药物组合物在多种治疗应用中的使用，包括使用大麻酸酯化合物和一个或多个额外治疗剂的联合疗法。
• Method for the treatment and prevention of cachexia
  申请人：Washington University

  公开号：US20030087942A1

  公开（公告）日：2003-05-08

  Cachexia, including anorexia and other forms of weight loss, is a frequent complication of acute and chronic infections, and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. The present invention includes methods for the treatment or prevention of cachexic conditions while maintaining the production of factors essential for infection control through the administration of an effective amount of a cyclooxygenase-2 selective inhibiting compound.

  消瘦症，包括厌食和其他形式的体重减轻，是急性和慢性感染的常见并发症，由细胞因子、前列腺素和其他炎症介质的诱导引起，这些介质对病原体清除至关重要。本发明包括通过给予有效量的环氧合酶-2选择性抑制化合物来治疗或预防消瘦症状，同时保持对感染控制至关重要的因子的产生的方法。