3-{[(4,6-dimethylpyrimidin-2-yl)sulfanyl]acetyl}benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-{[(4,6-dimethylpyrimidin-2-yl)sulfanyl]acetyl}benzenesulfonamide
• 英文别名: 3-[2-(4,6-Dimethylpyrimidin-2-yl)sulfanylacetyl]benzenesulfonamide；3-[2-(4,6-dimethylpyrimidin-2-yl)sulfanylacetyl]benzenesulfonamide
• 化学式: C₁₄H₁₅N₃O₃S₂
• 分子量: 337.423
• InChiKey: IJMXBTRCOPBDDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(2-溴乙酰基)苯磺酰胺 、 4,6-二甲基-2-巯基嘧啶 在 sodium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以80%的产率得到3-{[(4,6-dimethylpyrimidin-2-yl)sulfanyl]acetyl}benzenesulfonamide
  参考文献：
  名称：

  Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII

  摘要：

  Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzene-sulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.029

文献信息

• Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII
  作者：Edita Čapkauskaitė、Asta Zubrienė、Alexey Smirnov、Jolanta Torresan、Miglė Kišonaitė、Justina Kazokaitė、Joana Gylytė、Vilma Michailovienė、Vaida Jogaitė、Elena Manakova、Saulius Gražulis、Sigitas Tumkevičius、Daumantas Matulis

  DOI：10.1016/j.bmc.2013.09.029

  日期：2013.11

  Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzene-sulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms. (C) 2013 Elsevier Ltd. All rights reserved.