4-Hydroxy-3,5-dimethyl-phenylacetonitril | 1610-87-3

• 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: 4-Hydroxy-3,5-dimethyl-phenylacetonitril
• 英文别名: (3,5-dimethyl-4-hydroxy-phenyl)-acetonitrile；2-(4-hydroxy-3,5-dimethylphenyl)acetonitrile
• CAS: 1610-87-3
• 化学式: C₁₀H₁₁NO
• 分子量: 161.203
• InChiKey: JOXVSUUABHLJFJ-UHFFFAOYSA-N

物化性质

• 熔点：
  80.5-81 °C
• 沸点：
  311.5±37.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-3,5-dimethyl-phenylacetonitril 在 potassium hydroxide 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 24.0h， 生成 (4-羟基-3,5-二甲基苯基)乙酸
  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
• 作为产物：
  描述：

  4-[(二甲基氨基)甲基]-2,6-二甲苯酚 以 乙醚 、 乙醇 为溶剂， 反应 48.0h， 生成 4-Hydroxy-3,5-dimethyl-phenylacetonitril
  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

• Synthesis of Novel Benzylimidazolines Possessing Antihypertensive and Sedative Activity
  作者：Donald Cairns、Walter Sneader

  DOI：10.1002/ardp.19893220702

  日期：——

  produce new long acting local anaesthetics, a number of novel benzylimidazoline derivatives were synthesised and tested for local anaesthetic activity, vasoconstrictor effect and ease of displacement of p‐aminoclonidine. The synthesis is shown in Scheme 1. ‐ The synthesised compounds do not exhibit a significant local anaesthetic effect, but display an antihypertensive action with considerable α‐2 adrenoceptor

  在生产新型长效局部麻醉剂的研究过程中，合成了许多新型苄基咪唑啉衍生物，并测试了其局部麻醉活性、血管收缩作用和对氨基可乐定的易置换性。合成过程如图 1 所示。 - 合成的化合物不表现出显着的局部麻醉作用，但显示出具有相当大的 α-2 肾上腺素受体结合亲和力的抗高血压作用。
• 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。
• Polyphenylenether-Polykondensat-Blockcopolymere und Verfahren zu ihrer Herstellung
  申请人：HÜLS AKTIENGESELLSCHAFT

  公开号：EP0391030A2

  公开（公告）日：1990-10-10

  2.1 Aufgabe der Erfindung war die Entwicklung einer einfachen Synthese neuer Polyphenylenether-Polykondensat-Blockcopoly­merer, die weitestgehend frei von Homopolymeren anfallen sollten. 2.2 Die Aufgabe wurde durch ein Verfahren gelöst, das aus folgen­den Schritten besteht: - man stellt zunächst ein neuartiges Polykondensat her, das phenolische Endgruppen mit einer Fähigkeit zur oxidativen Kupplung besitzt; - dieses Polykondensat wird als Comonomeres bei der oxidati­ven Kupplung substituierter Phenole eingesetzt. 2.3 Die erfindungsgemäßen Blockcopolymere können für sich alleine oder als Zusatz für thermoplastische Formmassen verwendet werden.

  2.1 本发明的任务是开发一种新的聚苯醚-聚缩醛嵌段共聚物的简单合成方法，这种共聚物基本上不含均聚物。 2.2 本发明的任务是通过以下步骤解决的： - 首先，生产出一种新型聚缩聚物，这种聚缩聚物的酚醛末端基团具有氧化偶联能力； - 在取代酚的氧化偶联过程中，将这种聚缩醛用作共聚单体。 2.3 本发明的嵌段共聚物可单独使用，也可作为热塑性模塑料的添加剂使用。
• Blockcopolymere auf Basis von Polyphenylenethern und Polykondensaten sowie Verfahren zu ihrer Herstellung
  申请人：HÜLS AKTIENGESELLSCHAFT

  公开号：EP0391031A2

  公开（公告）日：1990-10-10

  2.1 Aufgabe der Erfindung war die Entwicklung einer einfachen Synthese neuer Polyphenylenether-Polykondensat-Blockcopolymerer. 2.2 Die Aufgabe wurde durch ein Verfahren gelöst, das aus folgenden Schritten besteht: - man stellt durch oxidative Kupplung eines Gemisches aus 90,0 - 99,8 Mol-% eines substituierten Phenols und 10,0 - 0,2 Mol-% eines funktionalisierten Phenols einen Poly­phenylenether mit einer funktionellen Endgruppe her; - anschließend führt man in Gegenwart dieses funktionalisier­ten Polyphenylenethers eine Polykondensation geeigneter Monomerer durch. 2.3 Die erfindungsgemäßen Blockcopolymere können für sich alleine oder als Zusatz für thermoplastische Formmassen verwendet werden.

  2.1 本发明的任务是开发一种新型聚苯醚-聚缩醛嵌段共聚物的简单合成方法。 2.2 本发明通过以下步骤解决了这一问题： - 通过氧化偶联 90.0 - 99.8 摩尔%的取代苯酚和 10.0 - 0.2 摩尔%的官能化苯酚混合物，制备具有官能末端基团的聚苯醚； - 然后在该官能化聚苯醚的存在下，对合适的单体进行缩聚。 2.3 本发明的嵌段共聚物可单独使用，也可作为热塑性模塑料的添加剂使用。