P903 | 110380-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: P903
• 英文别名: 4-[(Phenylethynyl)sulfonyl]morpholine；4-(2-phenylethynylsulfonyl)morpholine
• CAS: 110380-99-9
• 化学式: C₁₂H₁₃NO₃S
• 分子量: 251.306
• InChiKey: IFKMRZXTNDAEPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  P903 生成 4-((Z)-2-Phenyl-ethenesulfonyl)-morpholine
  参考文献：
  名称：

  BRIENE, MARIE-JOSEPHE;VARECH, DANIEL;LECLERCQ, MARTINE;JACQUES, JEAN;BADE+, J. MED. CHEM., 30,(1987) N 12, 2232-2239

  摘要：

  DOI：
• 作为产物：
  描述：

  4-methanesulfonylmorpholine 在 正丁基锂 、 2-氯-1-甲基吡啶碘化物 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 P903
  参考文献：
  名称：

  取代乙炔磺酰胺的简单通用合成

  摘要：

  通过两步操作制备了各种取代的2-芳基乙炔磺酰胺：1.通过适当的甲磺酰胺碳负离子与取代的苯甲酸酯反应制备2-氧代-2-芳基乙磺酰胺，2.通过2-脱水生成的酮氯-N-甲基吡啶碘化物/ NEt 3。

  DOI：

  10.1016/s0040-4039(00)97493-8

文献信息

• Risk of Late-Onset Alzheimer's Disease by Plasma Cholesterol: Rational<i>In Silico</i>Drug Investigation of Pyrrole-Based HMG-CoA Reductase Inhibitors
  作者：Sajad Shahbazi、Jagdeep Kaur、Ananya Kuanar、Dattatreya Kar、Shikha Singh、Ranbir Chander Sobti

  DOI：10.1089/adt.2017.804

  日期：2017.11

  blood cholesterol. Selective HMGCR inhibitor drugs such as statins, which increase the catabolism of plasma LDL and reduce the plasma concentration of cholesterol, have been investigated as a possible treatment for AD. In the present study, we have identified the binding modes of 22 various derivatives of 3-sulfamoylpyrroles 16, prepared via a [3 + 2] cycloaddition of a münchnone with a sulfonamide-substituted

  阿尔茨海默氏病（AD）是享誉全球的进行性神经退行性疾病，是痴呆症的最常见病因。胆固醇代谢在AD发病机理中的重要作用已有几项研究，表明高浓度的血清胆固醇会增加AD的风险。3-羟-3-甲基戊二酰辅酶A还原酶（HMGCR）通过甲羟戊酸途径中的HMG-CoA转化为甲羟戊酸来催化血浆胆固醇和其他类异戊二烯的生物合成。通常，血浆LDL降解会导致HGMCR抑制而使血浆胆固醇水平下调，但在异常情况下（例如，高血糖），HMGCR过度活化会导致血液胆固醇失控。选择性HMGCR抑制剂药物，例如他汀类药物，已经研究了增加血浆LDL分解代谢并降低血浆胆固醇浓度的药物，可以作为AD的治疗方法。在本研究中，我们已经确定了22种3-氨磺酰基吡咯16衍生物的结合模式，这是通过使用有效的生物计算工具，通过将Münchnone与磺酰胺取代的炔烃进行[3 + 2]环加成而制备的。在22种配体中，代号为5b，5c，5d，5i和5j
• Baudin, Jean-Bernard; Julia, Sylvestre A.; Wang, Yuan, Bulletin de la Societe Chimique de France, 1995, vol. 132, p. 952 - 962
  作者：Baudin, Jean-Bernard、Julia, Sylvestre A.、Wang, Yuan

  DOI：——

  日期：——
• Hepatoselectivity of statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors
  作者：William K.C. Park、Robert M. Kennedy、Scott D. Larsen、Steve Miller、Bruce D. Roth、Yuntao Song、Bruce A. Steinbaugh、Kevin Sun、Bradley D. Tait、Mark C. Kowala、Bharat K. Trivedi、Bruce Auerbach、Valerie Askew、Lisa Dillon、Jeffrey C. Hanselman、Zhiwu Lin、Gina H. Lu、Andrew Robertson、Catherine Sekerke

  DOI：10.1016/j.bmcl.2007.11.124

  日期：2008.2

  4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3 + 2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development. (C) 2007 Elsevier Ltd. All rights reserved.
• [EN] PYRROLE-BASED HMG-COA REDUCTASE INHIBITORS<br/>[FR] INHIBITEURS NOUVEAUX DE L'HMG-COA REDUCTASE A BASE DE PYRROLE
  申请人：WARNER LAMBERT CO

  公开号：WO2005014539A3

  公开（公告）日：2005-05-12
• New antifilarial agents. 1. Epoxy sulfonamides and ethynesulfonamides
  作者：Marie Josephe Brienne、Daniel Varech、Martine Leclercq、Jean Jacques、Nathalie Radembino、Christine Dessalles、Georges Mahuzier、Chantal Gueyouche、Christian Bories

  DOI：10.1021/jm00395a010

  日期：1987.12

  Two series of 2-substituted 1,2-epoxyethanesulfonamides 2 and ethynesulfonamides 5 were synthesized and evaluated for their antifilarial activity. The trans epoxides 2T were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. The cis isomers 2c were obtained from ethynesulfonamides 5 by semihydrogenation followed by KOCl epoxidation. 2-Substituted ethynesulfonamides 5 were synthesized from appropriate trans-ethenesulfonamides by a bromination/dehydrobromination sequence. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinema dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the epoxides 2T and acetylenic derivatives 5 bearing a 2-aryl substituent were active in vitro. Among these compounds, four epoxides 2T and one acetylenic derivative 5 showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chemical stability of the epoxy sulfonamides 2T. Despite this limitation, the activities observed in this reliable animal model suggest further development and testing of both series 2T and 5 as macrofilaricides.