2-chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide
• 英文别名: E11-8；2-Chloro-4-[(Pyrimidin-2-Ylsulfanyl)acetyl]benzenesulfonamide；2-chloro-4-(2-pyrimidin-2-ylsulfanylacetyl)benzenesulfonamide
• 化学式: C₁₂H₁₀ClN₃O₃S₂
• 分子量: 343.815
• InChiKey: ZQEDEEFNLDNUEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 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：

  4-(2-bromoacetyl)-2-chlorobenzenesulfonamide 、 2-巯基嘧啶 在 sodium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以81%的产率得到2-chloro-4-[(pyrimidin-2-ylsulfanyl)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

• Carbonic anhydrase enzymes for regulating mast cell hematopoiesis and type 2 inflammation
  申请人：Rutgers, The State University of New Jersey

  公开号：US10758537B2

  公开（公告）日：2020-09-01

  The invention provides methods and compositions that are useful for treating allergic diseases, bacterial infections, fungal infections, viral infections, mastocytosis, mast cell-mediated inflammation and parasite infections (e.g., helminth infections).

  本发明提供了可用于治疗过敏性疾病、细菌感染、真菌感染、病毒感染、肥大细胞增多症、肥大细胞介导的炎症和寄生虫感染（如蠕虫感染）的方法和组合物。
• CARBONIC ANHYDRASE ENZYMES FOR REGULATING MAST CELL HEMATOPOIESIS AND TYPE 2 INFLAMMATION
  申请人：Rutgers, the State University of New Jersey

  公开号：US20210052590A1

  公开（公告）日：2021-02-25

  The invention provides methods and compositions that are useful for treating allergic diseases, bacterial infections, fungal infections, viral infections, mastocytosis, mast cell-mediated inflammation and parasite infections (e.g., helminth infections).
• 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.