BAS3014820

• 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: BAS3014820
• 英文别名: N-(4-(2-(1H-indol-3-yl)thiazol-4-yl)phenyl)acetamide；Acetamide, N-[4-[2-(1H-indol-3-yl)thiazol-4-yl]phenyl]-；N-[4-[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]phenyl]acetamide
• 化学式: C₁₉H₁₅N₃OS
• 分子量: 333.414
• InChiKey: BQFPOGGYFJVAGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-[4-(2-溴乙酰基)苯基)乙酰胺 、 1H-吲哚-3-羰基羧酸酰铵 以 乙醇 为溶剂， 反应 2.5h， 以45%的产率得到BAS3014820
  参考文献：
  名称：

  [EN] SMALL-MOLECULE UT-A-SELECTIVE UREA TRANSPORT INHIBITORS
  [FR] INHIBITEURS DE TRANSPORT D'URÉE SÉLECTIFS UT-A À PETITES MOLÉCULES

  摘要：

  本文提供了一些尿素转运体A抑制剂化合物，可用于产生强烈的利尿反应，并可用于治疗与心血管、肾脏和代谢性疾病、紊乱和病症相关的难治性水肿。

  公开号：

  WO2015172065A1

文献信息

• [EN] SMALL-MOLECULE UT-A-SELECTIVE UREA TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT D'URÉE SÉLECTIFS UT-A À PETITES MOLÉCULES
  申请人：UNIV CALIFORNIA

  公开号：WO2015172065A1

  公开（公告）日：2015-11-12

  Provided herein are compounds that are urea transporter-A inhibitors that are useful for producing a strong diuretic response and may be used for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

  本文提供了一些尿素转运体A抑制剂化合物，可用于产生强烈的利尿反应，并可用于治疗与心血管、肾脏和代谢性疾病、紊乱和病症相关的难治性水肿。
• Small-molecule UT-A-selective urea transport inhibitors
  申请人：The Regents of the University of California

  公开号：US11123340B2

  公开（公告）日：2021-09-21

  Provided herein are compounds that are urea transporter-A inhibitors that are useful for producing a strong diuretic response and may be used for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

  本文提供的化合物是尿素转运体-A 抑制剂，可产生强烈的利尿反应，可用于治疗与心血管、肾脏和代谢疾病、失调和病症相关的难治性水肿。
• SMALL-MOLECULE UT-A-SELECTIVE UREA TRANSPORT INIHIBITORS
  申请人：The Regents of the University of California

  公开号：US20170239235A1

  公开（公告）日：2017-08-24

  Provided herein are compounds that are urea transporter-A inhibitors that are useful for producing a strong diuretic response and may be used for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.
• SMALL-MOLECULE UT-A-SELECTIVE UREA TRANSPORT INHIBITORS
  申请人：The Regents of the University of California

  公开号：US20200016147A1

  公开（公告）日：2020-01-16

  Provided herein are compounds that are urea transporter-A inhibitors that are useful for producing a strong diuretic response and may be used for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.
• Diuresis and reduced urinary osmolality in rats produced by small‐molecule UT‐A‐selective urea transport inhibitors
  作者：Cristina Esteva‐Font、Onur Cil、Puay‐Wah Phuan、Tao Su、Sujin Lee、Marc O. Anderson、A. S. Verkman

  DOI：10.1096/fj.14-253872

  日期：2014.9

  Urea transport (UT) proteins of the UT-A class are expressed in epithelial cells in kidney tubules, where they are required for the formation of a concentrated urine by countercurrent multiplication. Here, using a recently developed high-throughput assay to identify UT-A inhibitors, a screen of 50,000 synthetic small molecules identified UT-A inhibitors of aryl-thiazole, gamma-sultambenzosulfonamide, aminocarbonitrile butene, and 4-isoxazolamide chemical classes. Structure-activity analysis identified compounds that inhibited UT-A selectively by a noncompetitive mechanism with IC50 down to similar to 1 mu M. Molecular modeling identified putative inhibitor binding sites on rat UT-A. To test compound efficacy in rats, formulations and administration procedures were established to give therapeutic inhibitor concentrations in blood and urine. We found that intravenous administration of an indole thiazole or a gamma-sultambenzosulfonamide at 20 mg/kg increased urine output by 3-5-fold and reduced urine osmolality by similar to 2-fold compared to vehicle control rats, even under conditions of maximum antidiuresis produced by 1-deamino-8-D-arginine vasopressin (DDAVP). The diuresis was reversible and showed urea > salt excretion. The results provide proof of concept for the diuretic action of UT-A-selective inhibitors. UT-A inhibitors are first in their class salt-sparing diuretics with potential clinical indications in volume-overload edemas and high-vasopressin- associated hyponatremias.