6-methyl-3,4-methylenedioxyphenylsulfonylhydrazine | 246033-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 6-methyl-3,4-methylenedioxyphenylsulfonylhydrazine
• 英文别名: 6-methyl-3,4-methylenedioxyphenylsulphonylhydrazine；6-methyl-3,4-methylenedioxy-benzenesulfonylhydrazide；6-Methyl-1,3-benzodioxole-5-sulfonohydrazide；6-methyl-1,3-benzodioxole-5-sulfonohydrazide
• CAS: 246033-27-2
• 化学式: C₈H₁₀N₂O₄S
• 分子量: 230.244
• InChiKey: OQIIFMCBXMUONJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  99
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-methyl-3,4-methylenedioxyphenylsulfonylhydrazine 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 3.5h， 生成 LASSBio-1632
  参考文献：
  名称：

  Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies

  摘要：

  Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-alpha production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112492
• 作为产物：
  描述：

  6-methyl-3,4-methylenedioxyphenylsulfonyl chloride 在 一水合肼 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以92%的产率得到6-methyl-3,4-methylenedioxyphenylsulfonylhydrazine
  参考文献：
  名称：

  天然黄樟脑中新型芳基磺酰胺衍生物的合成及抗血小板评价。

  摘要：

  在旨在合成和可能评估新型抗血小板原型化合物的药理学研究计划，探索分子设计的生物等渗原理的研究计划范围内，我们在本文中描述了新的芳基磺酰胺衍生物的合成，其结构与已知的血栓烷A2受体拮抗剂相似。用于获得本文所述新化合物的合成途径始于黄樟脑（一种丰富的巴西天然产物），其存在于S木油（Ocotea pretiosa）中。通过使用ADP，胶原蛋白，花生四烯酸和U46619诱导的兔PRP，通过血小板凝集抑制试验对这些新型芳基磺酰胺化合物进行的初步评估，结果确定了N- [2-（4-羧基甲氧基苯基）乙基]- 6-甲基-3，

  DOI：

  10.1016/s0031-6865(99)00004-7

文献信息

• Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole##This paper represents contribution # 36 of the LASSBio, UFRJ (Br.) (LASSBio, http://acd.ufrj.br/≈pharma/lassbio); For contribution # 35, see [24].
  作者：Patrícia C. Lima、Lídia M. Lima、Kelli Cristine M. da Silva、Paulo Henrique O. Léda、Ana Luisa P. de Miranda、Carlos A.M. Fraga、Eliezer J. Barreiro

  DOI：10.1016/s0223-5234(00)00120-3

  日期：2000.2

  Anew series of antinociceptive compounds belonging to the N-acylarylhydrazone (NAH) class were synthesized from natural safrole (7). The most analgesic derivative represented by 10f, [(4'-N,N-dimethylaminobenzylidene-3-(3', 4'-methylenedioxyphenyl)propionylhydrazine], was more potent than dipyrone and indomethacin, used as standards. The NAH compounds described herein were structurally planned by molecular

  从天然黄樟脑合成了一系列新的N-酰基芳基hydr（NAH）类抗伤害感受化合物（7）。以10f表示的最止痛衍生物，[（4'-N，N-二甲基氨基苄叉基-3-（3'，4'-亚甲基二氧苯基）丙酰肼]]比双嘧啶和消炎痛更有效，用作标准品。我们通过分子杂交和经典生物立体异构策略对先前报道的止痛NAH进行结构规划，以鉴定N-酰基芳基hydr部分的药效学作用并研究这些系列中的构效关系（SAR）。
• Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole
  作者：Lı́dia M. Lima、Cláudia B. Ormelli、Fernanda F. Brito、Ana L.P. Miranda、Carlos A.M. Fraga、Eliezer J. Barreiro

  DOI：10.1016/s0031-6865(99)00004-7

  日期：1999.6

  aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A2 receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant

  在旨在合成和可能评估新型抗血小板原型化合物的药理学研究计划，探索分子设计的生物等渗原理的研究计划范围内，我们在本文中描述了新的芳基磺酰胺衍生物的合成，其结构与已知的血栓烷A2受体拮抗剂相似。用于获得本文所述新化合物的合成途径始于黄樟脑（一种丰富的巴西天然产物），其存在于S木油（Ocotea pretiosa）中。通过使用ADP，胶原蛋白，花生四烯酸和U46619诱导的兔PRP，通过血小板凝集抑制试验对这些新型芳基磺酰胺化合物进行的初步评估，结果确定了N- [2-（4-羧基甲氧基苯基）乙基]- 6-甲基-3，
• Synthesis and Antinociceptive Profile of Novel Acidic Sulphonylhydrazone Derivatives From Natural Safrole
  作者：L.M. Lima、E.G. Amarante、A.L.P. Miranda、C.A.M. Fraga、E.J. Barreiro

  DOI：10.1211/146080899128734370

  日期：1999.12.1
• Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies
  作者：Isabelle Karine da Costa Nunes、Everton Tenório de Souza、Italo Rossi Roseno Martins、Gisele Barbosa、Manoel Oliveira de Moraes Junior、Millena de Melo Medeiros、Sheyla Welma Duarte Silva、Tatiane Luciano Balliano、Bagnólia Araújo da Silva、Patrícia Machado Rodrigues Silva、Vinicius de Frias Carvalho、Marco Aurélio Martins、Lidia Moreira Lima

  DOI：10.1016/j.ejmech.2020.112492

  日期：2020.10

  Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-alpha production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability. (C) 2020 Elsevier Masson SAS. All rights reserved.