3-(1-Benzofuran-2-ylsulfonyl)-6-methoxypyridazine | 1027430-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-(1-Benzofuran-2-ylsulfonyl)-6-methoxypyridazine
• CAS: 1027430-36-9
• 化学式: C₁₃H₁₀N₂O₄S
• 分子量: 290.299
• InChiKey: AMPUNIOAARVESL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  90.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(1-Benzofuran-2-ylsulfonyl)-6-methoxypyridazine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 6-(benzofuran-2-sulfonyl)-2H-pyridazin-3-one
  参考文献：
  名称：

  A Highly Selective, Non-Hydantoin, Non-Carboxylic Acid Inhibitor of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models:  6-(5-Chloro-3-methylbenzofuran- 2-sulfonyl)-2-H-pyridazin-3-one

  摘要：

  We report here on the discovery path that led to a structurally unprecedented non-hydantoin, non-carboxylic acid aldose reductase inhibitor, 24, which shows remarkably potent oral activity in normalizing elevated sorbitol levels and, more significantly, fructose levels in the sciatic nerve of chronically diabetic rats, with ED90 values of 0.8 and 3 mpk, respectively. It is well absorbed in rats (oral bioavailability, 98%) and has a long plasma t(1/2) (26 +/- 3 h).

  DOI：

  10.1021/jm034065z
• 作为产物：
  描述：

  3-氯-6-甲氧基哒嗪 在 正丁基锂 、 potassium hydrogen bifluoride 、 水 、 氯 、 硫脲 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 丁酮 为溶剂， 生成 3-(1-Benzofuran-2-ylsulfonyl)-6-methoxypyridazine
  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