3-Hydroxy-6-benzylsulfonyl-pyridazin | 92016-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-Hydroxy-6-benzylsulfonyl-pyridazin
• 英文别名: 6-phenylmethanesulfonyl-2H-pyridazin-3-one；E2RC5V5Tta；3-benzylsulfonyl-1H-pyridazin-6-one
• CAS: 92016-73-4
• 化学式: C₁₁H₁₀N₂O₃S
• 分子量: 250.278
• InChiKey: QUZYPEPCSQAPEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  84
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-Methoxy-6-benzylsulfonyl-pyridazin 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-Hydroxy-6-benzylsulfonyl-pyridazin
  参考文献：
  名称：

  A Novel Series of Non-Carboxylic Acid, Non-Hydantoin Inhibitors of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models:  6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and Congeners

  摘要：

  Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2H-pyridazin-3-one, 81, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t(1/2) (26 +/- 3 h).

  DOI：

  10.1021/jm050462t

文献信息

• A Novel Series of Non-Carboxylic Acid, Non-Hydantoin Inhibitors of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models:  6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2<i>H</i>-pyridazin-3-one and Congeners
  作者：Banavara L. Mylari、Sandra J. Armento、David A. Beebe、Edward L. Conn、James B. Coutcher、Michael S. Dina、Melissa T. O'Gorman、Michael C. Linhares、William H. Martin、Peter J. Oates、David A. Tess、Gregory J. Withbroe、William J. Zembrowski

  DOI：10.1021/jm050462t

  日期：2005.10.1

  Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2H-pyridazin-3-one, 81, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t(1/2) (26 +/- 3 h).