6-(4-amino-2,6-dichlorophenoxy)-4-isopropyl-2-methylpyridazin-3(2H)-one | 920509-68-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(4-amino-2,6-dichlorophenoxy)-4-isopropyl-2-methylpyridazin-3(2H)-one
• 英文别名: 6-(4-amino-2,6-dichlorophenoxy)-4-isopropyl-2-methyl-2H-pyridazin-3-one；6-(4-Amino-2,6-dichloro-phenoxy)-4-isopropyl-2-methyl-2H-pyridazin-3-one；6-(4-amino-2,6-dichlorophenoxy)-2-methyl-4-propan-2-ylpyridazin-3-one
• CAS: 920509-68-8
• 化学式: C₁₄H₁₅Cl₂N₃O₂
• 分子量: 328.198
• InChiKey: ACRWOHPZAJEREA-UHFFFAOYSA-N

物化性质

• 沸点：
  462.9±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-amino-2,6-dichlorophenoxy)-4-isopropyl-2-methylpyridazin-3(2H)-one 在 4-二甲氨基吡啶 、 盐酸羟胺 、 sodium acetate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 28.83h， 生成 3-(1-((3,5-dichloro-4-((5-isopropyl-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)amino)ethyl)-1,2,4-oxadiazol-5(4H)-one
  参考文献：
  名称：

  与恶二唑酮酸等排物的选择性甲状腺激素受体β激动剂。

  摘要：

  在三碘甲腺嘌呤类似物中使用恶二唑酮酸等排酮可产生有效且选择性的甲状腺激素受体β激动剂。选定的实例在大鼠高胆固醇血症模型中显示出良好的体内功效。在饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠模型中进一步分析了一种化合物，该化合物在肝脂肪变性和纤维化中均显示出强大的靶标参与性和明显的组织学改善。

  DOI：

  10.1016/j.bmcl.2020.127465
• 作为产物：
  描述：

  2,6-二氯-4-氨基苯酚 在 copper(l) iodide 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 、 正丁胺 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 39.0h， 生成 6-(4-amino-2,6-dichlorophenoxy)-4-isopropyl-2-methylpyridazin-3(2H)-one
  参考文献：
  名称：

  Discovery of 2-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β Agonist in Clinical Trials for the Treatment of Dyslipidemia

  摘要：

  The beneficial effects of thyroid hormone (TH) on lipid levels are primarily due to its action at the thyroid hormone receptor beta (THR-beta) in the liver, while adverse effects, including cardiac effects, are mediated by thyroid hormone receptor alpha (THR-alpha). A pyridazinone series has been identified that is significantly more THR-beta selective than earlier analogues. Optimization of this series by the addition of a cyanoazauracil substituent improved both the potency and selectivity and led to MGL-3196 (53), which is 28-fold selective for THR-beta over THR-alpha in a functional assay. Compound 53 showed outstanding safety in a rat heart model and was efficacious in a preclinical model at doses that showed no impact on the central thyroid axis. In reported studies in healthy volunteers, 53 exhibited an excellent safety profile and decreased LDL cholesterol (LDL-C) and triglycerides (TG) at once daily oral doses of 50 mg or higher given for 2 weeks.

  DOI：

  10.1021/jm4019299

文献信息

• THYROID HORMONE RECEPTOR BETA AGONIST COMPOUNDS
  申请人：Terns, Inc.

  公开号：US20200115362A1

  公开（公告）日：2020-04-16

  Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.

  本文提供了化合物，优选为甲状腺激素受体β（THR beta）激动剂化合物，其组成，其制备方法，激动THR beta的方法以及治疗由THR beta介导的疾病的方法。
• THYROID HORMONE ANALOGS
  申请人：Haynes Nancy-Ellen

  公开号：US20090005383A1

  公开（公告）日：2009-01-01

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto.

  本文提供了公式（I）的化合物，以及其药学上可接受的盐，其中取代基如说明书所披露的那样。这些化合物和含有它们的药物组合物对于治疗肥胖症、高脂血症、高胆固醇血症和糖尿病以及其他相关疾病和疾病非常有用，并且可能对于其他疾病，如NASH，动脉粥样硬化，心血管疾病，甲状腺功能减退症，甲状腺癌和其他相关的疾病和疾病也有用。
• Thyroid hormone analogs
  申请人：Haynes Nancy-Ellen

  公开号：US20070032494A1

  公开（公告）日：2007-02-08

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto.

  本文提供的化合物公式(I)及其药学上可接受的盐，其中取代基如规范中所述。这些化合物及其含有的药物组成物，可用于治疗肥胖症、高脂血症、高胆固醇血症、糖尿病和其他相关疾病，也可能对NASH、动脉粥样硬化、心血管疾病、甲状腺功能减退症、甲状腺癌和其他相关疾病有用。
• Thyroid hormone receptor beta agonist compounds
  申请人：Terns, Inc.

  公开号：US10800767B2

  公开（公告）日：2020-10-13

  Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, and methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.

  本文提供的是化合物，优选甲状腺激素受体 beta（THR beta）激动剂化合物、其组合物及其制备方法，以及激动 THR beta 的方法和治疗 THR beta 介导的疾病的方法。
• WO2007/9913
  申请人：——

  公开号：——

  公开（公告）日：——