descyano-bimakalim-6-sulfonic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: descyano-bimakalim-6-sulfonic acid
• 英文别名: 2,2-Dimethyl-4-(2-oxopyridin-1-yl)chromene-6-sulfonic acid
• 化学式: C₁₆H₁₅NO₅S
• 分子量: 333.365
• InChiKey: ACKCROGXSYYORR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  descyano-bimakalim-6-sulfochloride 在 水 作用下， 反应 1.0h， 生成 descyano-bimakalim-6-sulfonic acid
  参考文献：
  名称：

  K_ATPchannel openers of the benzopyran type reach their binding site via the cytosol

  摘要：

  Background and purpose:ATP‐sensitive K+ (KATP) channels are composed of pore‐forming subunits (Kir6.x) and of sulphonylurea receptors (SUR). Both sulphonylureas and KATP channel openers act by binding to SUR. Sulphonylureas reach their binding site from the cytosol but it remains unknown whether this holds for openers too.Experimental approach:A poorly membrane‐permeant sulphonic acid derivative of the benzopyran‐type opener, bimakalim, was synthesized, descyano‐bimakalim‐6‐sulphonic acid (BMSA). Binding of BMSA and bimakalim was compared in membranes and intact cells expressing the Kir6.2/SUR2B channel and channel opening was compared in inside‐out patches and whole cells.Key results:In membranes, bimakalim and BMSA bound to Kir6.2/SUR2B with Ki values of 61 nM and 4.3 μM, showing that the negative charge decreased affinity 69‐fold. In intact cells, however, binding of BMSA was much weaker than in membranes (75‐fold) whereas that of bimakalim was unchanged. The Ki value of BMSA decreased with increasing incubation time. In inside‐out patches, bimakalim (1 μM) and BMSA (100 μM) opened the Kir6.2/SUR2B channel closed by MgATP to a similar degree whereas in whole‐cell experiments, only bimakalim was effective.Conclusions and implications:Despite its negative charge, BMSA is an effective channel opener. The fact that BMSA binds and acts more effectively when applied to the inner side of the cell membrane shows that benzopyran openers reach their binding site at SUR from the cytosol. This suggests that the binding pocket of SUR is only open on the cytoplasmic side.British Journal of Pharmacology (2006) 149, 199–205. doi:10.1038/sj.bjp.0706858

  DOI：

  10.1038/sj.bjp.0706858

文献信息

• K_ATPchannel openers of the benzopyran type reach their binding site via the cytosol
  作者：D Stephan、E Salamon、H Weber、U Russ、H Lemoine、U Quast

  DOI：10.1038/sj.bjp.0706858

  日期：2006.9

  Background and purpose:ATP‐sensitive K+ (KATP) channels are composed of pore‐forming subunits (Kir6.x) and of sulphonylurea receptors (SUR). Both sulphonylureas and KATP channel openers act by binding to SUR. Sulphonylureas reach their binding site from the cytosol but it remains unknown whether this holds for openers too.Experimental approach:A poorly membrane‐permeant sulphonic acid derivative of the benzopyran‐type opener, bimakalim, was synthesized, descyano‐bimakalim‐6‐sulphonic acid (BMSA). Binding of BMSA and bimakalim was compared in membranes and intact cells expressing the Kir6.2/SUR2B channel and channel opening was compared in inside‐out patches and whole cells.Key results:In membranes, bimakalim and BMSA bound to Kir6.2/SUR2B with Ki values of 61 nM and 4.3 μM, showing that the negative charge decreased affinity 69‐fold. In intact cells, however, binding of BMSA was much weaker than in membranes (75‐fold) whereas that of bimakalim was unchanged. The Ki value of BMSA decreased with increasing incubation time. In inside‐out patches, bimakalim (1 μM) and BMSA (100 μM) opened the Kir6.2/SUR2B channel closed by MgATP to a similar degree whereas in whole‐cell experiments, only bimakalim was effective.Conclusions and implications:Despite its negative charge, BMSA is an effective channel opener. The fact that BMSA binds and acts more effectively when applied to the inner side of the cell membrane shows that benzopyran openers reach their binding site at SUR from the cytosol. This suggests that the binding pocket of SUR is only open on the cytoplasmic side.British Journal of Pharmacology (2006) 149, 199–205. doi:10.1038/sj.bjp.0706858