6-(3,4-dichloro-benzenesulfonyl)-2H-pyridazin-3-one

• 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: 6-(3,4-dichloro-benzenesulfonyl)-2H-pyridazin-3-one
• 英文别名: 3-(3,4-dichlorophenyl)sulfonyl-1H-pyridazin-6-one
• 化学式: C₁₀H₆Cl₂N₂O₃S
• 分子量: 305.141
• InChiKey: QDLUZHBVOVEPQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  3,4-二氯苯硫酚 在 盐酸 、 sodium methylate 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 为溶剂， 生成 6-(3,4-dichloro-benzenesulfonyl)-2H-pyridazin-3-one
  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

• Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors
  申请人：——

  公开号：US20030004139A1

  公开（公告）日：2003-01-02

  This invention relates to novel sulfonyl pyridazinone compounds useful as aldose reductase inhibitors in the treatment or prevention of certain complications arising from diabetes mellitus, pharmaceutical compositions comprising the sulfonyl pyridazinone, pharmaceutical compositions comprising a combination of the sulfonyl pyridazinone together with a second pharmaceutical agent, therapeutic methods comprising the administration of the sulfonyl pyridazinone compounds, therapeutic methods comprising the administration of the sulfonyl pyridazinone compounds in combination with a second pharmaceutical agent and compounds useful as intermediates for preparing the sulfonyl pyridazinone compounds of this invention.

  这项发明涉及一种新型的磺酰基吡啶并酮化合物，可用作醛糖还原酶抑制剂，用于治疗或预防由糖尿病引起的某些并发症，包括含有磺酰基吡啶并酮的药物组合物，含有磺酰基吡啶并酮与第二药物剂的药物组合物，包括给予磺酰基吡啶并酮化合物的治疗方法，以及包括给予磺酰基吡啶并酮化合物与第二药物剂的组合的治疗方法，以及用作制备本发明磺酰基吡啶并酮化合物的中间体的化合物。
• Therapies for tissue damage resulting from ischemia
  申请人：——

  公开号：US20030008871A1

  公开（公告）日：2003-01-09

  This invention relates to therapeutic methods for treatment or prevention of tissue damage resulting from ischemia in mammals.

  该发明涉及治疗方法，用于治疗或预防哺乳动物因缺血而导致的组织损伤。
• [EN] COMBINATIONS OF ALDOSE REDUCTASE INHIBITORS AND CYCLOOXYGENASE-2 INHIBITORS<br/>[FR] COMBINAISONS D'INHIBITEURS D'ALDOSE REDUCTASE ET INHIBITEURS DE CYCLO-OXYGENASE 2
  申请人：PFIZER PROD INC

  公开号：WO2002087584A1

  公开（公告）日：2002-11-07

  This invention relates to pharmaceutical compositions and kits comprising pyridazinone compounds and cyclooxygenase-2 inhibitors, therapeutic methods of treatment or prevention of certain complications arising from diabetes mellitus in mammals and therapeutic methods of treatment or prevention of cardiac tissue ischemia in mammals.

  本发明涉及含有吡啶并咪唑酮化合物和环氧合酶-2抑制剂的药物组合物和套装，以及治疗或预防哺乳动物糖尿病引起的某些并发症和心脏组织缺血的治疗方法。
• Therapies relating to combinations of aldose reductase inhibitors and cyclooxygenase-2
  申请人：Pfizer Inc

  公开号：US20040198740A1

  公开（公告）日：2004-10-07

  This invention relates to pharmaceutical compositions and kits comprising pyridazinone compounds and cyclooxygenase-2 inhibitors, therapeutic methods of treatment or prevention of certain complications arising from diabetes mellitus in mammals and therapeutic methods of treatment or prevention of cardiac tissue ischemia in mammals.

  本发明涉及药物组合物和工具包，包括吡啶并咪唑酮化合物和环氧合酶-2抑制剂，用于治疗或预防哺乳动物糖尿病引起的某些并发症的治疗方法和用于治疗或预防哺乳动物心脏组织缺血的治疗方法。
• THERAPIES RELATING TO COMBINATIONS OF ALDOSE REDUCTASE INHIBITORS AND CYCLOOXYGENASE-2 INHIBITORS
  申请人：Mylari L. Banavara

  公开号：US20050004124A1

  公开（公告）日：2005-01-06

  This invention relates to pharmaceutical compositions and kits comprising pyridazinone compounds and cyclooxygenase-2 inhibitors, therapeutic methods of treatment or prevention of certain complications arising from diabetes mellitus in mammals and therapeutic methods of treatment or prevention of cardiac tissue ischemia in mammals.

  本发明涉及含有吡啶并咪唑酮化合物和环氧合酶-2抑制剂的药物组合物和工具包，以及哺乳动物糖尿病引起的某些并发症的治疗或预防方法和哺乳动物心脏组织缺血的治疗或预防方法。