thiophene-2-thioacetonitrile | 26031-45-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: thiophene-2-thioacetonitrile
• 英文别名: (2-Thienylthio)acetonitrile；2-thiophen-2-ylsulfanylacetonitrile
• CAS: 26031-45-8
• 化学式: C₆H₅NS₂
• 分子量: 155.244
• InChiKey: VWQZUPDUGIISLF-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于氯仿、DCM、DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  thiophene-2-thioacetonitrile 在 sodium ethanolate 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.75h， 生成 3-(thiophene-2-sulfonyl)-4H-thieno[2,3-e][1,2,3]triazolo-[1,5-a]pyrimidin-5-one
  参考文献：
  名称：

  Nanomolar Potency and Metabolically Stable Inhibitors of Kidney Urea Transporter UT-B

  摘要：

  Urea transporters, which include UT-B in kidney microvessels, are potential targets for development of drugs with a novel diuretic ('urearetic') mechanism. We recently identified, by high-throughput screening, a triazolothienopyrimidine UT-B inhibitor, 1, that selectively and reversibly inhibited urea transport with IC50 = 25.1 nM and reduced urinary concentration in mice (Yao et al. J. Am. Soc. Nephrol., in press). Here, we analyzed 273 commercially available analogues of 1 to establish a structure-activity series and synthesized a targeted library of 11 analogues to identify potent, metabolically stable UT-B inhibitors. The best compound, {3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-y1}thiophen-2-ylmethylamine, 3k, had IC50 of 23 and 15 nM for inhibition of urea transport by mouse and human UT-B, respectively, and similar to 40-fold improved in vitro metabolic stability compared to 1. In mice, 3k accumulated in kidney and urine and reduced maximum urinary concentration. Triazolothienopyrimidines may be useful for therapy of diuretic-refractory edema in heart and liver failure.

  DOI：

  10.1021/jm300491y
• 作为产物：
  描述：

  2-噻吩硫醇 、 溴乙腈 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 thiophene-2-thioacetonitrile
  参考文献：
  名称：

  Nanomolar Potency and Metabolically Stable Inhibitors of Kidney Urea Transporter UT-B

  摘要：

  Urea transporters, which include UT-B in kidney microvessels, are potential targets for development of drugs with a novel diuretic ('urearetic') mechanism. We recently identified, by high-throughput screening, a triazolothienopyrimidine UT-B inhibitor, 1, that selectively and reversibly inhibited urea transport with IC50 = 25.1 nM and reduced urinary concentration in mice (Yao et al. J. Am. Soc. Nephrol., in press). Here, we analyzed 273 commercially available analogues of 1 to establish a structure-activity series and synthesized a targeted library of 11 analogues to identify potent, metabolically stable UT-B inhibitors. The best compound, {3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-y1}thiophen-2-ylmethylamine, 3k, had IC50 of 23 and 15 nM for inhibition of urea transport by mouse and human UT-B, respectively, and similar to 40-fold improved in vitro metabolic stability compared to 1. In mice, 3k accumulated in kidney and urine and reduced maximum urinary concentration. Triazolothienopyrimidines may be useful for therapy of diuretic-refractory edema in heart and liver failure.

  DOI：

  10.1021/jm300491y

文献信息

• Novel thiophene derivatives and their preparation
  申请人：Schering Aktiengesellschaft

  公开号：US04031236A1

  公开（公告）日：1977-06-21

  Thiophene derivatives of the formula ##STR1## IN WHICH R.sub.x is --S--CHR.sub.5 --CONHOH or --S--CHR.sub.5 -5-tetrazolyl in which R.sub.5 is H or alkyl of 1-6 carbon atoms and R.sub.y is 0-2 of alkyl or alkoxy of 1-6 carbon atoms or halogen, and their pharmacologically acceptable salts with bases, possess antilipolytic activity.

  该文献描述的是一类硫吡啶衍生物，其化学式为##STR1##其中R.sub.x为--S--CHR.sub.5 --CONHOH或--S--CHR.sub.5 -5-四唑基，其中R.sub.5为H或1-6碳原子的烷基，R.sub.y为0-2个1-6碳原子的烷基、烷氧基或卤素，以及它们与碱的药理学可接受盐具有抗脂解活性。
• 10.1021/acs.jafc.4c00461
  作者：Zhou, Cong、Kong, Yijin、Zhang, Huihui、Zhai, Na、Li, Zhong、Qian, Xuhong、Liu, Zewen、Cheng, Jiagao

  DOI：10.1021/acs.jafc.4c00461

  日期：——

  Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate

  为了寻找低蜜蜂毒性的新型新烟碱类杀虫剂，通过子结构剪接策略合理设计了一系列具有低蜜蜂毒性的噻唑烷结构的化合物，并评价了其杀虫活性。最佳化合物A24和A29对豆蚜的LC 50值分别为30.01和17.08 mg/L。对爪蟾卵母细胞进行的电生理研究表明，化合物A29作用于昆虫nAChR，EC 50值为50.11 μM。对接结合模式分析表明， A29通过与 D_Arg55、D_Leu102 和 D_Val114 残基的氢键与Lymnaea stagnalis乙酰胆碱结合蛋白结合。量子力学计算表明，与蜜蜂高毒性吡虫啉相比， A29具有更高的最高占据分子轨道（HOMO）能量和更低的垂直电离势（IP）值，显示出潜在的低蜜蜂毒性。蜜蜂毒性预测模型也表明A29对蜜蜂无毒。我们目前的工作确定了一种创新的杀虫支架，可能有助于进一步探索低蜂毒新烟碱类杀虫剂。
• US4031236A
  申请人：——

  公开号：US4031236A

  公开（公告）日：1977-06-21
• Nanomolar Potency and Metabolically Stable Inhibitors of Kidney Urea Transporter UT-B
  作者：Marc O. Anderson、Jicheng Zhang、Yan Liu、Chenjuan Yao、Puay-Wah Phuan、A. S. Verkman

  DOI：10.1021/jm300491y

  日期：2012.6.28

  Urea transporters, which include UT-B in kidney microvessels, are potential targets for development of drugs with a novel diuretic ('urearetic') mechanism. We recently identified, by high-throughput screening, a triazolothienopyrimidine UT-B inhibitor, 1, that selectively and reversibly inhibited urea transport with IC50 = 25.1 nM and reduced urinary concentration in mice (Yao et al. J. Am. Soc. Nephrol., in press). Here, we analyzed 273 commercially available analogues of 1 to establish a structure-activity series and synthesized a targeted library of 11 analogues to identify potent, metabolically stable UT-B inhibitors. The best compound, 3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-y1}thiophen-2-ylmethylamine, 3k, had IC50 of 23 and 15 nM for inhibition of urea transport by mouse and human UT-B, respectively, and similar to 40-fold improved in vitro metabolic stability compared to 1. In mice, 3k accumulated in kidney and urine and reduced maximum urinary concentration. Triazolothienopyrimidines may be useful for therapy of diuretic-refractory edema in heart and liver failure.