5-((5-(pyridin-3-yl)thiophen-2-yl)methylene)-2-thioxoimidazolidin-4-one | 1313397-31-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-((5-(pyridin-3-yl)thiophen-2-yl)methylene)-2-thioxoimidazolidin-4-one
• 英文别名: (E,Z)-5-((5-(pyridin-3-yl)thiophen-2-yl)methylene)-2-thioxoimidazolidin-4-one；5-[(5-Pyridin-3-ylthiophen-2-yl)methylidene]-2-sulfanylideneimidazolidin-4-one；5-[(5-pyridin-3-ylthiophen-2-yl)methylidene]-2-sulfanylideneimidazolidin-4-one
• CAS: 1313397-31-7
• 化学式: C₁₃H₉N₃OS₂
• 分子量: 287.366
• InChiKey: PSQKRXABUNNCAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-硫代乙内酰脲 、 5-吡啶-3-噻吩-2-甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 5-((5-(pyridin-3-yl)thiophen-2-yl)methylene)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  已知岩藻糖苷酶抑制剂的生物电子等排修饰发现α-的新颖抑制剂升-fucosidase †

  摘要：

  已知岩藻糖苷酶抑制剂A和B的生物立体异构修饰产生了三种新类型的分子，分别属于呋喃吡啶二酮，硫代乙内酰脲和乙内酰脲化学分型的4b，5c和6a，它们可能与α- L-岩藻糖苷酶（牛肾来源）结合。分子对接揭示并比较了4b，5c和6a与A和B之间的假定结合相互作用与α- L同源模型的活性位点-岩藻糖苷酶。基于此初步研究，设计和合成了基于呋喃吡啶二酮，硫代乙内酰脲和乙内酰脲的小分子文库，然后对其体外筛选抗α- L-岩藻糖苷酶（牛肾来源）产生了一种有效的IC抑制剂（化合物4e）约0.7μM中的50。当针对健康的哺乳动物COS-1细胞进行测试时，化合物4e不具有细胞毒性。反应动力学研究表明它是一种混合抑制剂。最后化合物4a，b，e和f带有呋喃并吡啶二酮基序的α，也显示出对MCF 7乳腺癌细胞增殖的实质性抑制。

  DOI：

  10.1039/c6ra24939f

文献信息

• COMPOUNDS, PREPARATION AND USES THEREOF
  申请人：Spicer Julie Ann

  公开号：US20130065897A1

  公开（公告）日：2013-03-14

  The present invention provides novel compounds of the Formula I, pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.

  本发明提供了公式I的新化合物，包括这些化合物的制药组合物以及使用这些化合物作为抑制穿孔素活性的药剂或药物的方法，以及用于治疗处于风险或易感疾病或紊乱，或具有与不良穿孔素活性相关的疾病或紊乱的受试者。
• Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin
  作者：Julie A. Spicer、Gersande Lena、Dani M. Lyons、Kristiina M. Huttunen、Christian K. Miller、Patrick D. O’Connor、Matthew Bull、Nuala Helsby、Stephen M. F. Jamieson、William A. Denny、Annette Ciccone、Kylie A. Browne、Jamie A. Lopez、Jesse Rudd-Schmidt、Ilia Voskoboinik、Joseph A. Trapani

  DOI：10.1021/jm401604x

  日期：2013.12.12

  A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perform. Structure activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perform protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (<= 2.5 mu M) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T-1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).
• Bioisosteric modification of known fucosidase inhibitors to discover a novel inhibitor of α-<scp>l</scp>-fucosidase
  作者：Chandramohan Bathula、Shreemoyee Ghosh、Santanu Hati、Sayantan Tripathy、Shailja Singh、Saikat Chakrabarti、Subhabrata Sen

  DOI：10.1039/c6ra24939f

  日期：——

  on furopyridinedione, thiohydantoin and hydantoin, followed by their in vitro screening against α-L-fucosidase (bovine kidney origin) generated a potent inhibitor (compound 4e) with IC50 of ∼0.7 μM. Compound 4e possessed no cytotoxic properties when tested against healthy mammalian COS-1 cells. Reaction kinetics study suggested it to be a mixed inhibitor. Finally compounds 4a, b, e and f, bearing the

  已知岩藻糖苷酶抑制剂A和B的生物立体异构修饰产生了三种新类型的分子，分别属于呋喃吡啶二酮，硫代乙内酰脲和乙内酰脲化学分型的4b，5c和6a，它们可能与α- L-岩藻糖苷酶（牛肾来源）结合。分子对接揭示并比较了4b，5c和6a与A和B之间的假定结合相互作用与α- L同源模型的活性位点-岩藻糖苷酶。基于此初步研究，设计和合成了基于呋喃吡啶二酮，硫代乙内酰脲和乙内酰脲的小分子文库，然后对其体外筛选抗α- L-岩藻糖苷酶（牛肾来源）产生了一种有效的IC抑制剂（化合物4e）约0.7μM中的50。当针对健康的哺乳动物COS-1细胞进行测试时，化合物4e不具有细胞毒性。反应动力学研究表明它是一种混合抑制剂。最后化合物4a，b，e和f带有呋喃并吡啶二酮基序的α，也显示出对MCF 7乳腺癌细胞增殖的实质性抑制。