BM 8 | 137783-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: BM 8
• 英文别名: N-((4-(cyclohexylamino)pyrid-3-yl)sulfonyl)-N'-cycloheptylurea；1-Cycloheptyl-3-[4-(cyclohexylamino)pyridin-3-yl]sulfonylurea
• CAS: 137783-20-1
• 化学式: C₁₉H₃₀N₄O₃S
• 分子量: 394.538
• InChiKey: TYKQJYSEBSXMKR-UHFFFAOYSA-N

物化性质

• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (4-(cyclohexylamino)pyrid-3-yl)sulfonamide 在 吡啶 作用下， 以 甲苯 为溶剂， 反应 5.33h， 生成 BM 8
  参考文献：
  名称：

  Synthesis and pharmacology of pyrid-3-yl sulfonylureas and thioureas as astrocytic Na+ 2C1− K+ cotransporter inhibitors

  摘要：

  The pharmacology of lipophilic 4-arylamino- and 4-cycloalkylaminopyrid-3-ylsulfonyl(thio)ureas and their synthesis designed from torasemide are described. These compounds could lead to a method of inhibiting the astrocytic Na+ 2Cl(-) K+ cotransporter and thus treating cerebral edema. Their lipophilicity and ionization constants were determined. Seven lipophilic compounds (17, 18, 22, 23, 24, 32 and 36) exhibited a high inhibitory potency (IC50 < 10 mu M) and had lost the diuretic properties of torasemide. One of them, N-([4-(cycloheptylamino)pyrid-3-yl]sulfonyl)-N'-cycloheptylurea 17 (0.1-1 mg/kg) was found to increase the gasp delay in hypoxia-exposed mice. In preliminary experiments, 17 (1-2.5 mg/kg) strongly reduced the morbidity and mortality rate of gerbils after permanent left carotid artery ligation. In-vitro experiments confirmed its antiedematous activity.

  DOI：

  10.1016/0223-5234(94)90145-7

文献信息

• Design, Synthesis and Biological Activity of a Series of Torasemide Derivatives, Potent Blockers of the Na+ 2Cl− K+ Co-transporter: In-vitro Study
  作者：B Masereel、E Lohrmann、M Schynts、B Pirotte、R Greger、J Delarg

  DOI：10.1111/j.2042-7158.1992.tb05470.x

  日期：2011.4.12

  Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl− K+ co-transport in the thick ascending limb of the loop of Henlé has been performed in order to obtain new long-acting diuretics. The aim of this study was to decrease the metabolism of the drug and to slow down its rate of excretion by increasing its hydrophobicity. The present study describes the synthesis and the inhibitory potency of new torasemide derivatives in the bioassay system of the cortical thick ascending limb of rabbit. A correlation between the lipophilicity (log P') of these substances and their activity as inhibitors of the Na+ Cl− K+ co-transporter was observed. The present design led to compounds more active than torasemide. Structure-activity relationships permit us to propose an interaction model between torasemide derivatives and the Na+ 2Cl− K+ co-transport system of the cortical thick ascending limb.

  摩尔卡西尼酸分子的药物调节，一种抑制髓袢厚壁升支肢上的Na+ 2Cl− K+共转运的环利尿剂已经进行，以获得新的长效利尿剂。本研究旨在通过增加其疏水性来降低药物的代谢并减慢其排泄速率。本研究描述了新摩尔卡西尼酸衍生物在兔子皮质厚壁升支肢生物测定系统中的合成和抑制效力。观察到这些物质的亲脂性（log P'）与它们作为Na+ Cl− K+共转运抑制剂的活性之间的相关性。目前的设计导致比摩尔卡西尼酸更活跃的化合物。结构活性关系使我们能够提出摩尔卡西尼酸衍生物与皮质厚壁升支肢的Na+ 2Cl− K+共转运系统之间的相互作用模型。
• Nouveaux dérivés de la pyridylsulfonylurée et de la pyridylsulfonylthiourée leur procédé de préparation et les compositions pharmaceutiques que les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0445039B1

  公开（公告）日：1994-06-08
• US5166162A
  申请人：——

  公开号：US5166162A

  公开（公告）日：1992-11-24
• Synthesis and pharmacology of pyrid-3-yl sulfonylureas and thioureas as astrocytic Na+ 2C1− K+ cotransporter inhibitors
  作者：B Masereel、P Renard、M Schynts、B Pirotte、P de Tullio、J Delarge

  DOI：10.1016/0223-5234(94)90145-7

  日期：1994.1

  The pharmacology of lipophilic 4-arylamino- and 4-cycloalkylaminopyrid-3-ylsulfonyl(thio)ureas and their synthesis designed from torasemide are described. These compounds could lead to a method of inhibiting the astrocytic Na+ 2Cl(-) K+ cotransporter and thus treating cerebral edema. Their lipophilicity and ionization constants were determined. Seven lipophilic compounds (17, 18, 22, 23, 24, 32 and 36) exhibited a high inhibitory potency (IC50 < 10 mu M) and had lost the diuretic properties of torasemide. One of them, N-([4-(cycloheptylamino)pyrid-3-yl]sulfonyl)-N'-cycloheptylurea 17 (0.1-1 mg/kg) was found to increase the gasp delay in hypoxia-exposed mice. In preliminary experiments, 17 (1-2.5 mg/kg) strongly reduced the morbidity and mortality rate of gerbils after permanent left carotid artery ligation. In-vitro experiments confirmed its antiedematous activity.