[3-(4-(4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydro-pyran-4-carbonyl)-piperazin-1-yl)-propyl]-trimethyl-ammonium trifluoroacetate salt | 1369390-22-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [3-(4-(4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydro-pyran-4-carbonyl)-piperazin-1-yl)-propyl]-trimethyl-ammonium trifluoroacetate salt
• 英文别名: 3-[4-[4-[[2,4-Dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]propyl-trimethylazanium;2,2,2-trifluoroacetate
• CAS: 1369390-22-6
• 化学式: C₂F₃O₂*C₃₄H₄₆Cl₂N₅O₅S
• 分子量: 820.758
• InChiKey: KXFIUNOZXUZGAY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  54
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(3-methoxy-3-oxopropyl)piperazine-1-carboxylate 在 盐酸 、 lithium aluminium tetrahydride 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.58h， 生成 [3-(4-(4-[2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-benzenesulfonylamino]-tetrahydro-pyran-4-carbonyl)-piperazin-1-yl)-propyl]-trimethyl-ammonium trifluoroacetate salt
  参考文献：
  名称：

  Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine

  摘要：

  A series of alpha,alpha-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B-2(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.036

文献信息

• Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine
  作者：Christopher I. Fincham、Alessandro Bressan、Piero D’Andrea、Alessandro Ettorre、Sandro Giuliani、Sandro Mauro、Stefania Meini、Marielle Paris、Laura Quartara、Cristina Rossi、Antonella Squarcia、Claudio Valenti、Fattori Daniela、Carlo Alberto Maggi

  DOI：10.1016/j.bmc.2012.01.036

  日期：2012.3

  A series of alpha,alpha-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B-2(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results. (C) 2012 Elsevier Ltd. All rights reserved.