2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(4-sulfamoylbenzyl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(4-sulfamoylbenzyl)acetamide
• 英文别名: 2-(2,4-dioxopyrimidin-1-yl)-N-[(4-sulfamoylphenyl)methyl]acetamide
• 化学式: C₁₃H₁₄N₄O₅S
• 分子量: 338.344
• InChiKey: YOLWLZFDBXYATH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(2,4-二氧代嘧啶-1-基)乙酸 、 mafenide hydrochloride 在 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(4-sulfamoylbenzyl)acetamide
  参考文献：
  名称：

  新型含氮碱的磺酰胺碳酸酐酶IX抑制剂的发现

  摘要：

  将嘌呤/嘧啶部分作为尾部掺入经典的苯磺酰胺支架中，可提供两个系列的人（h）碳酸酐酶（CA，EC 4.2.1.1）抑制剂。根据分子杂交方法设计化合物，以调节与不同CA同工酶的相互作用，并以平行和协同模式利用尿嘧啶和腺嘌呤衍生物的抗肿瘤作用来抑制与肿瘤相关的hCA IX。研究了磺酰胺作为四种同工型的抑制剂，即胞质hCA I / II和跨膜hCA IV / IX。抑制曲线取决于连接两个药效基团的间隔子的长度和位置。X射线晶体学证实了抑制剂与hCA II和hCA IX模拟物的结合模式。评估具有最佳hCA IX抑制功效的化合物对HT-29结肠癌细胞系的抗增殖活性。这体外结果表明，多种作用机制是该化合物的细胞毒性功效的原因。

  DOI：

  10.1021/acsmedchemlett.7b00399

文献信息

• Benzenesulfonamides incorporating nitrogenous bases show effective inhibition of β-carbonic anhydrases from the pathogenic fungi Cryptococcus neoformans, Candida glabrata and Malassezia globosa
  作者：Silvia Bua、Sameh M. Osman、Zeid AlOthman、Claudiu T. Supuran、Alessio Nocentini

  DOI：10.1016/j.bioorg.2019.01.030

  日期：2019.5

  There is an urgent need for new chemotherapic agents to treat human fungal infections due to emerging and spreading globally resistance mechanisms. Among the new targets that have been recently investigated for the development of antifungal drugs there are the metallo-enzymes Carbonic Anhydrases (CAs, EC 4.2.1.1). The inhibition of the beta-CAs identified in many pathogenic fungi leads to an impairment of parasite growth and virulence, which in turn leads to a significant anti-infective effect. Based on antifungal nucleoside antibiotics, the inhibition of the beta-CAs from the resistance-showing fungi Candida glabrata (CgNce103), Cryptococcus neoformans (Can2) and Malasszia globosa (MgCA) with a series of benzenesulfonamides bearing nitrogenous bases, such as uracil and adenine, is here reported. Many such compounds display low nanomolar (< 100 nM) inhibitory potency against Can2 and CgNce103, whereas the activity of MgCA is considerably less affected (inhibition constants in the range 138.8-5601.5 nM). The beta-CAs inhibitory data were compared with those against alpha-class human ubiquitous isoforms. Interesting selective inhibitory activities for the target fungal CAs over hCA I and II were reported, which make nitrogenous base benzenesulfonamides interesting tools and leads for further investigations in search of new antifungal with innovative mechanisms of action.
• Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases
  作者：Alessio Nocentini、Silvia Bua、Carrie L. Lomelino、Robert McKenna、Marta Menicatti、Gianluca Bartolucci、Barbara Tenci、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Paola Gratteri、Claudiu T. Supuran

  DOI：10.1021/acsmedchemlett.7b00399

  日期：2017.12.14

  human (h) carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The compounds were designed according to the molecular hybridization approach, in order to modulate the interaction with different CA isozymes and exploit the antitumor effect of uracil and adenine derivatives in parallel and synergic mode to the inhibition of the tumor-associated hCA IX. The sulfonamides were investigated as inhibitors of four

  将嘌呤/嘧啶部分作为尾部掺入经典的苯磺酰胺支架中，可提供两个系列的人（h）碳酸酐酶（CA，EC 4.2.1.1）抑制剂。根据分子杂交方法设计化合物，以调节与不同CA同工酶的相互作用，并以平行和协同模式利用尿嘧啶和腺嘌呤衍生物的抗肿瘤作用来抑制与肿瘤相关的hCA IX。研究了磺酰胺作为四种同工型的抑制剂，即胞质hCA I / II和跨膜hCA IV / IX。抑制曲线取决于连接两个药效基团的间隔子的长度和位置。X射线晶体学证实了抑制剂与hCA II和hCA IX模拟物的结合模式。评估具有最佳hCA IX抑制功效的化合物对HT-29结肠癌细胞系的抗增殖活性。这体外结果表明，多种作用机制是该化合物的细胞毒性功效的原因。