3(2H)-哒嗪硫酮,6-甲氧基- | 1430-25-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3(2H)-哒嗪硫酮,6-甲氧基-
• 英文名称: 3-mercapto-6-methoxy pyridazine
• 英文别名: 3-mercapto-6-methoxypyridazine；6-methoxypyridazine-3-thiol；3-methoxy-6-mercaptopyridazine；6-methoxy-pyridazine-3-thiol；6-methoxy-2H-pyridazine-3-thione；6-Mercapto-3-methoxy-pyridazin；3-methoxy-1H-pyridazine-6-thione
• CAS: 1430-25-7
• 化学式: C₅H₆N₂OS
• 分子量: 142.181
• InChiKey: NWUYAYVDHURYQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  65.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3(2H)-哒嗪硫酮,6-甲氧基- 在 sodium hypochlorite 、 potassium hydrogen bifluoride 、 四丁基硫酸氢铵 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.67h， 以73%的产率得到6-methoxy-pyridazine-3-sulfonyl fluoride
  参考文献：
  名称：

  杂芳基硫醇方便地制备杂芳基磺酰胺和磺酰氟

  摘要：

  杂芳族硫醇可通过使用3.3当量的次氯酸钠水溶液在低温（−25°C）下氧化为磺酰氯。该反应是快速的，避免了使用氯气，并且成功地使用了以前发现的底物，该底物在其他方法下几乎没有或根本没有提供磺酰胺产物。该方法允许制备磺酰氟，该磺酰氟足够稳定以被纯化和储存，从而使其成为潜在的有用的单体，可用于平行化学研究中。

  DOI：

  10.1021/jo052164+
• 作为产物：
  描述：

  3-氯-6-甲氧基哒嗪 在 硫脲 作用下， 以 丁酮 为溶剂， 生成 3(2H)-哒嗪硫酮,6-甲氧基-
  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

文献信息

• Pyridazinone aldose reductase inhibitors
  申请人：——

  公开号：US20020143017A1

  公开（公告）日：2002-10-03

  The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention also relates to other combinations with the ARIs of this invention, including combinations with adendsine agonists; NHE-1 inhibitors; glycogen phosphorylase inhibitors; selective serotonin reuptake inhibitors; GABA agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; phosphodiesterase-5 inhibitors; and to glucose lowering agents.

  本发明涉及新型吡啶二酮化合物，包括这些化合物的药物组合物，以及使用这些化合物和组合物来抑制醛糖还原酶，降低山梨醇水平，从而降低果糖水平，并/或治疗或预防哺乳动物中的糖尿病并发症，如糖尿病神经病变、糖尿病视网膜病变、糖尿病肾病、糖尿病心肌病、糖尿病微血管病和糖尿病大血管病。本发明还涉及一种为非糖尿病患者提供心脏保护的方法。本发明还涉及包括本发明的醛糖还原酶抑制剂（ARI）和山梨醇脱氢酶抑制剂的组合的药物组合物和套装，以及使用这些组合物或套装来治疗或预防哺乳动物中上述糖尿病并发症的方法。本发明还涉及与本发明的ARI的其他组合，包括与腺苷激动剂的组合；NHE-1 抑制剂；糖原磷酸化酶抑制剂；选择性5-羟色胺再摄取抑制剂；GABA 激动剂；降压药物；3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂；磷酸二酯酶-5 抑制剂；以及降糖药物。
• Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
  作者：Tim Markovic、Benjamin N. Rocke、David C. Blakemore、Vincent Mascitti、Michael C. Willis

  DOI：10.1021/acs.orglett.7b02944

  日期：2017.11.17

  heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including

  一系列5元和6元杂环衍生的亚磺酸盐显示是使用Pd（0）催化与芳基氯化物和溴化物的有效亲核偶联伙伴。使用最佳反应条件，特别是掺入P（t - Bu）2 Me衍生的Pd催化剂，可以在中等温度下进行反应，并可以包含各种敏感的官能团。具有挑战性的杂环亚磺酸盐，包括吡嗪，哒嗪，嘧啶，吡唑和咪唑，均表现出良好的性能。
• 3-Pyridazine derivatives and their use in rubber
  申请人：MONSANTO COMPANY

  公开号：EP0726255A3

  公开（公告）日：1997-03-26

  Thiols, disulfides and sulfenamides of certain pyridazines are effective accelerators in the sulfur vulcanization of rubber. These compounds, based on 3-pyridazine show improved rates of vulcanization and states of cure compared with known sulfenamide accelerators.

  某些吡啶并嗪的硫醇、二硫化物和硫酰胺是橡胶硫化的有效催化剂。这些化合物基于3-吡啶并嗪，与已知的硫酰胺催化剂相比，显示出更高的硫化速率和硫化状态。
• 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 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.

  本发明涉及治疗或预防哺乳动物缺血引起的组织损伤的治疗方法。

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