ethyl 3-(pyridin-4-yl)-4-(naphthalen-2-yl)-4-oxobutanoate | 629623-76-3

• 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: ethyl 3-(pyridin-4-yl)-4-(naphthalen-2-yl)-4-oxobutanoate
• 英文别名: ethyl 4-(naphthalen-2-yl)-4-oxo-3-(pyridin-4-yl)butanoate；4-naphthalen-2-yl-4-oxo-3-pyridin-4-yl-butyric acid ethyl ester；ethyl 4-naphthalen-2-yl-4-oxo-3-pyridin-4-ylbutanoate
• CAS: 629623-76-3
• 化学式: C₂₁H₁₉NO₃
• 分子量: 333.387
• InChiKey: XCHQMEYEMGTUNM-UHFFFAOYSA-N

物化性质

• 沸点：
  525.8±40.0 °C(Predicted)
• 密度：
  1.193±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(pyridin-4-yl)-4-(naphthalen-2-yl)-4-oxobutanoate 在 苄基三乙基氯化铵 、 溴 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 肼 、 三氯氧磷 作用下， 以 N-甲基吡咯烷酮 、 叔丁醇 为溶剂， 反应 22.5h， 生成 (R)-N¹-(6-Naphthalen-2-yl-5-pyridin-4-yl-pyridazin-3-yl)-3-phenyl-propane-1,2-diamine
  参考文献：
  名称：

  Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase

  摘要：

  Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.

  DOI：

  10.1016/j.bmcl.2005.02.010
• 作为产物：
  描述：

  4-甲基吡啶 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 18.75h， 生成 ethyl 3-(pyridin-4-yl)-4-(naphthalen-2-yl)-4-oxobutanoate
  参考文献：
  名称：

  Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase

  摘要：

  Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.

  DOI：

  10.1016/j.bmcl.2005.02.010

文献信息

• Substituted heterocyclic compounds and methods of use
  申请人：Cao Guo-Qiang

  公开号：US20050038010A1

  公开（公告）日：2005-02-17

  The present invention relates to compounds having the general formula or a pharmaceutically acceptable salt thereof, wherein R 1 is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R 1 is additionally substituted; and R 2 is a substituted C 1-6 alkyl. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

  本发明涉及具有一般式的化合物或其药学上可接受的盐，其中R1是饱和或不饱和的5、6或7元环，包含0、1、2或3个选自N、O和S的原子，环可以与苯并环融合，并且被0、1或2个氧代基取代，其中R1还被取代；而R2是取代的C1-6烷基。还包括一种预防或治疗炎症、类风湿性关节炎、帕吉特病、骨质疏松症、多发性骨髓瘤、葡萄膜炎、急性或慢性髓性白血病、胰岛素β细胞破坏、骨关节炎、类风湿脊柱炎、痛风性关节炎、炎症性肠病、成人呼吸窘迫综合症（ARDS）、牛皮癣、克罗恩病、过敏性鼻炎、溃疡性结肠炎、过敏性休克、接触性皮炎、哮喘、肌肉退化、消瘦症、Reiter综合症、1型糖尿病、2型糖尿病、骨吸收性疾病、移植物抗宿主反应、阿尔茨海默病、中风、心肌梗死、缺血再灌注损伤、动脉硬化、脑外伤、多发性硬化、脑疟疾、败血症、感染性休克、毒性休克综合征、发热、因HIV-1、HIV-2、HIV-3、巨细胞病毒（CMV）、流感、腺病毒、疱疹病毒或带状疱疹感染而导致的肌痛的哺乳动物中，通过给予上述化合物的有效量来实现。
• MAP KINASE MODULATORS AND USES THEREOF
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US20160130253A1

  公开（公告）日：2016-05-12

  The invention provides for novel MAP kinase inhibitors and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38α MAP kinase inhibitors. The invention further provides for methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease.

  本发明提供了新型的MAP激酶抑制剂和包含它们的组合物。在某些实施例中，MAP激酶抑制剂是p38α MAP激酶抑制剂。该发明还提供了治疗疾病的方法，包括给予MAP激酶抑制剂或包含MAP激酶抑制剂的组合物。在某些实施例中，该疾病是阿尔茨海默病，肌萎缩性侧索硬化症，亨廷顿病或帕金森病。
• PYRAZINE COMPOUNDS AS MAP KINASE MODULATORS AND USES THEREOF
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP3521284A1

  公开（公告）日：2019-08-07

  The invention provides novel MAP kinase inhibitors of formula (I) and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38a MAP kinase inhibitors. The invention further provides compounds (I) for use in the methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease. wherein X1 is CH and X2 is N.

  本发明提供了式(I)的新型MAP激酶抑制剂和包含其的组合物。在某些实施方案中，MAP 激酶抑制剂是 p38a MAP 激酶抑制剂。本发明进一步提供了化合物(I)用于治疗疾病的方法，包括施用MAP激酶抑制剂或包含MAP激酶抑制剂的组合物。在某些实施方案中，疾病是阿尔茨海默病、渐冻人症、亨廷顿氏病或帕金森氏病。 其中X1为CH，X2为N。
• MAP KINASE MODULATORS AND USES THEREOF IN THE TRETAMENT OF TAUOPATHIES
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP3842424A1

  公开（公告）日：2021-06-30

  The invention provides for novel MAP kinase inhibitors and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38a MAP kinase inhibitors. The invention further provides for methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease.

  本发明提供了新型 MAP 激酶抑制剂和包含这些抑制剂的组合物。在某些实施方案中，MAP 激酶抑制剂是 p38a MAP 激酶抑制剂。本发明进一步提供了治疗疾病的方法，包括给予 MAP 激酶抑制剂或包含 MAP 激酶抑制剂的组合物。在一些实施方案中，疾病是阿尔茨海默病、渐冻人症、亨廷顿氏病或帕金森氏病。
• MAP kinase modulators and uses thereof
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US10428047B2

  公开（公告）日：2019-10-01

  The invention provides for novel MAP kinase inhibitors and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38α MAP kinase inhibitors. The invention further provides for methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease.

  本发明提供了新型 MAP 激酶抑制剂和包含这些抑制剂的组合物。在某些实施方案中，MAP 激酶抑制剂是 p38α MAP 激酶抑制剂。本发明进一步提供了治疗疾病的方法，包括施用 MAP 激酶抑制剂或包含 MAP 激酶抑制剂的组合物。在某些实施方案中，疾病是阿尔茨海默病、渐冻人症、亨廷顿氏病或帕金森氏病。