6-methyl-3,4-methylenedioxyphenylsulfonyl chloride | 246033-22-7

• 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-methylenedioxyphenylsulfonyl chloride
• 英文别名: 2-methyl-4,5-methylenedioxy-phenyl-sulfonyl chloride；2-methyl-3,4-methylenedioxybenzenesulfonyl chloride；6-methyl-3,4-methylenedioxy-benzenesulfonyl chloride；6-methylbenzo[d][1,3]dioxole-5-sulfonyl chloride；6-methyl-2H-1,3-benzodioxole-5-sulfonyl chloride；6-methyl-1,3-benzodioxole-5-sulfonyl chloride
• CAS: 246033-22-7
• 化学式: C₈H₇ClO₄S
• mdl: MFCD19200482
• 分子量: 234.66
• InChiKey: XDFACGYICDTWAH-UHFFFAOYSA-N

物化性质

• 沸点：
  345.1±42.0 °C(Predicted)
• 密度：
  1.528±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methyl-3,4-methylenedioxyphenylsulfonyl chloride 在 碳酸氢钠 、 potassium carbonate 作用下， 以 乙酸乙酯 、 丙酮 为溶剂， 反应 38.0h， 生成 N-{2-[4-(1-methoxycarbonylethoxy)phenyl]ethyl}-6-methyl-3,4-methylenedioxyphenyl sulfonamido
  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
• 作为产物：
  描述：

  3,4-(亚甲二氧基)甲苯 在 氯化亚砜 、 硫酸 、 溶剂黄146 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 6-methyl-3,4-methylenedioxyphenylsulfonyl chloride
  参考文献：
  名称：

  被设计为磷酸二酯酶4抑制剂的新型磺酰胺的合成，药理作用和对接研究。

  摘要：

  先前的研究表明，循环AMP的水平升高会下调肺部炎症变化，从而激发人们对磷酸二酯酶（PDE）4作为治疗靶标的兴趣。在这里，我们描述了设计为PDE4抑制剂的新型磺酰胺系列（5和6a-k）的合成，药理作用和对接特性。使用IMAP荧光偏振方案筛选化合物对人PDE4四种同工型的选择性。在A / J小鼠中研究了对变应原或LPS诱导的肺部炎症和气道高反应性（AHR）的影响，而甲苯噻嗪/氯胺酮诱导的麻醉试验被用作啮齿动物呕吐的行为相关因素。与咯利普兰相比，最有希望筛选的化合物6a（LASSBio-448）对PDE4D / PDE4A或PDE4D / PDE4B表现出更好的抑制指数。因此，对LASSBio-448的假定相互作用的对接分析显示，PDE4A和PDE4C的活性位点具有相似的姿势，但与PDE4B和PDE4D的取向略有不同。LASSBio-448（100 mg / kg，口服），在激发前1小时，抑制了

  DOI：

  10.1371/journal.pone.0162895

文献信息

• Design, Synthesis and Pharmacological Evaluation of Novel Conformationally Restricted N-arylpiperazine Derivatives Characterized as D2/D3 Receptor Ligands, Candidates for the Treatment of Neurodegenerative Diseases
  作者：Thayssa Tavares da Silva Cunha、Rafaela Ribeiro Silva、Daniel Alencar Rodrigues、Pedro de Sena Murteira Pinheiro、Thales Kronenberger、Carlos Maurício R. Sant’Anna、François Noël、Carlos Alberto Manssour Fraga

  DOI：10.3390/biom12081112

  日期：——

  play a key role in the treatment of such disorders. In this context, a novel series of conformationally restricted N-arylpiperazine derivatives (5a–f) with a good affinity for D2/D3 dopamine receptors is reported herein. Compounds were designed as interphenylene analogs of the drugs aripiprazole (2) and cariprazine (3), presenting a 1,3-benzodioxolyl subunit as a ligand of the secondary binding site of

  大多数神经退行性疾病是多因素的，与其发病机制相关的几种分子机制的发现不断推进。多巴胺和多巴胺能受体亚型涉及几种神经系统疾病的病理生理学，例如精神分裂症、抑郁症和药物成瘾。因此，多巴胺能系统和多巴胺受体配体在此类疾病的治疗中起关键作用。在这种情况下，一系列对 D 2 /D 3具有良好亲和力的新型构象受限的N-芳基哌嗪衍生物 ( 5a – f )本文报道了多巴胺受体。化合物被设计为药物阿立哌唑 (2) 和卡利拉嗪 (3) 的苯间苯类似物，呈现 1,3-苯并二氧戊环亚基作为这些受体二级结合位点的配体。使用经典方法以良好的收率合成了六种新的N-芳基哌嗪化合物，并进行了结合和鸟苷三磷酸 (GTP) 位移研究。发现靶受体的亲和力值低于 1 μM 和不同的内在功效谱。对接研究表明，化合物5a – f与多巴胺 D 2和 D 3呈现不同的结合模式受体，主要是由于对 2 和 3 的柔性间隔基施加的构象限制。
• 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.
• Synthesis and anti-platelet activity of novel arylsulfonate–acylhydrazone derivatives, designed as antithrombotic candidates
  作者：Lídia M. Lima、Flávia S. Frattani、Jean L. dos Santos、Helena C. Castro、Carlos Alberto M. Fraga、Russolina B. Zingali、Eliezer J. Barreiro

  DOI：10.1016/j.ejmech.2007.03.032

  日期：2008.2

  In this work, we describe a new class of promising anti-platelet drug candidates with significant antithrombotic activity in vivo. This new series of compounds was structurally planned by modification of known thrombin inhibitors based on the use of acylhydrazone subunit, as a non-peptide scaffold, and variations at PI moiety. Three different families of arylsulfonate-acylhydrazone derivatives were designed. The bioassays indicated the first class of derivatives represented by 4f (LASSBio-693) and 4j (LASSBio-743), which were active in inhibiting the platelet aggregation induced by thrombin. The second class represented by compounds 4e (LASSBio-774) and 4h (LASSBio-480) that selectively inhibit the platelet aggregation involving TXA(2) formation. Finally, the third class of derivatives was identified acting as a novel symbiotic agent able to inhibit the platelet aggregation induced by collagen or AA and by thrombin, represented by compounds 4b (LASSBio-694) and 4g (LASSBio-770). (c) 2007 Elsevier Masson SAS. All rights reserved.
• Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors
  作者：Isabelle Karine da Costa Nunes、Everton Tenório de Souza、Suzana Vanessa S. Cardozo、Vinicius de Frias Carvalho、Nelilma Correia Romeiro、Patrícia Machado Rodrigues e Silva、Marco Aurélio Martins、Eliezer J. Barreiro、Lídia Moreira Lima

  DOI：10.1371/journal.pone.0162895

  日期：——

  showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using

  先前的研究表明，循环AMP的水平升高会下调肺部炎症变化，从而激发人们对磷酸二酯酶（PDE）4作为治疗靶标的兴趣。在这里，我们描述了设计为PDE4抑制剂的新型磺酰胺系列（5和6a-k）的合成，药理作用和对接特性。使用IMAP荧光偏振方案筛选化合物对人PDE4四种同工型的选择性。在A / J小鼠中研究了对变应原或LPS诱导的肺部炎症和气道高反应性（AHR）的影响，而甲苯噻嗪/氯胺酮诱导的麻醉试验被用作啮齿动物呕吐的行为相关因素。与咯利普兰相比，最有希望筛选的化合物6a（LASSBio-448）对PDE4D / PDE4A或PDE4D / PDE4B表现出更好的抑制指数。因此，对LASSBio-448的假定相互作用的对接分析显示，PDE4A和PDE4C的活性位点具有相似的姿势，但与PDE4B和PDE4D的取向略有不同。LASSBio-448（100 mg / kg，口服），在激发前1小时，抑制了
• 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，