[3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e]-[1,2,3]triazolo[1,5-a]pyrimidin-5-yl]thiophen-2-ylmethylamine | 1383563-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: [3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e]-[1,2,3]triazolo[1,5-a]pyrimidin-5-yl]thiophen-2-ylmethylamine
• 英文别名: {3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-yl}thiophen-2-ylmethylamine；{3-[4-(1,1-Difluoroethyl)-benzenesulfonyl]-thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-yl}-thiophen-2-ylmethylamine；10-[4-(1,1-difluoroethyl)phenyl]sulfonyl-N-(thiophen-2-ylmethyl)-5-thia-1,8,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-7-amine
• CAS: 1383563-67-4
• 化学式: C₂₀H₁₅F₂N₅O₂S₃
• 分子量: 491.566
• InChiKey: GPUPXRRVLPBXMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-噻吩甲胺 、 3-((4-(1,1-difluoroethyl)phenyl)sulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-one 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 反应 1.0h， 以15%的产率得到[3-[4-(1,1-difluoroethyl)benzenesulfonyl]thieno[2,3-e]-[1,2,3]triazolo[1,5-a]pyrimidin-5-yl]thiophen-2-ylmethylamine
  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

• [EN] TRIAZOLOTHIENOPYRIMIDINE COMPOUND INHIBITORS OF UREA TRANSPORTERS AND METHODS OF USING INHIBITORS<br/>[FR] COMPOSÉS INHIBITEURS TRIAZOLOTHIÉNOPYRIMIDINES DE TRANSPORTEURS D'URÉE ET PROCÉDÉS D'UTILISATION DES INHIBITEURS
  申请人：UNIV CALIFORNIA

  公开号：WO2013148813A1

  公开（公告）日：2013-10-03

  Provided herein are small molecule triazolothienopyrimidine compounds that inhibit urea transport activity of solute transporters, particularly the UT-B transporter. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

  本文提供了一种小分子三唑并噻吩嘧啶化合物，可抑制溶质转运体的尿素转运活性，尤其是UT-B转运体。本文所描述的化合物可用于增加液体过载状态下的溶质清除，并用于治疗与心血管、肾脏和代谢性疾病、障碍和病况相关的顽固性水肿。
• TRIAZOLOTHIENOPYRIMIDINE COMPOUND INHIBITORS OF UREA TRANSPORTERS AND METHODS OF USING INHIBITORS
  申请人：Anderson Marc

  公开号：US20150057274A1

  公开（公告）日：2015-02-26

  Provided herein are small molecule triazolothienopyrimidine compounds that inhibit urea transport activity of solute transporters, particularly the UT-B transporter. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

  本文提供了一种小分子三唑噻吩嘧啶化合物，可抑制溶质转运体，特别是UT-B转运体的尿素转运活性。本文所描述的化合物可用于在液体过载状态下增加溶质清除，并用于治疗与心血管、肾脏和代谢性疾病、紊乱和情况相关的难治性水肿。
• US9303042B2
  申请人：——

  公开号：US9303042B2

  公开（公告）日：2016-04-05
• 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.