3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1-{4-[2-(piperidin-1-yl)ethoxy]naphthalen-1-yl}urea | 285983-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1-{4-[2-(piperidin-1-yl)ethoxy]naphthalen-1-yl}urea
• 英文别名: 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-piperidin-1-ylethoxy)naphthalen-1-yl]urea
• CAS: 285983-72-4
• 化学式: C₃₂H₃₉N₅O₂
• 分子量: 525.694
• InChiKey: RTGVWXYTMRGERL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氨基-1-萘酚 在 4-二甲氨基吡啶 、 sodium hydroxide 、 苄基三丁基氯化铵 、 碳酸氢钠 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 56.25h， 生成 3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1-{4-[2-(piperidin-1-yl)ethoxy]naphthalen-1-yl}urea
  参考文献：
  名称：

  Structure−Activity Relationships of the p38α MAP Kinase Inhibitor 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naph- thalen-1-yl]urea (BIRB 796)

  摘要：

  We report on the structure-activity relationships (SAR) of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]urea (BIRB 796), an inhibitor of p38alpha MAP kinase which has advanced into human clinical trials for the treatment of autoimmune diseases. Thermal denaturation was used to establish molecular binding affinities for this class of p38alpha inhibitors. The tert-butyl group remains a critical binding element by occupying a lipophilic domain in the kinase which is exposed upon rearrangement of the activation loop. An aromatic ring attached to N-2 of the pyrazole nucleus provides important pi-CH2 interactions with the kinase. The role of groups attached through an ethoxy group to the 4-position of the naphthalene and directed into the ATP-binding domain is elucidated. Pharmacophores with good hydrogen bonding potential, such as morpholine, pyridine, and imidazole, shift the melting temperature of p38alpha by 16-17 degreesC translating into K-d values of 50-100 pM. Finally, we describe several compounds that potently inhibit TNF-alpha production when dosed orally in mice.

  DOI：

  10.1021/jm030121k

文献信息

• Combination Therapy with p38 MAP Kinase Inhibitors and their Pharmaceutical Compositions
  申请人：SIMIANER Stefan

  公开号：US20070099832A1

  公开（公告）日：2007-05-03

  The present invention relates to pharmaceutical combinations therapies based on p38 kinase inhibitors and another active ingredient, pharmaceutical compositions comprising such combinations, processes for preparing them and their use in the treatment of cytokine mediated diseases.

  本发明涉及基于p38激酶抑制剂和另一种活性成分的药物组合疗法，包括这种组合物的药物组合物、制备它们的过程以及它们在治疗细胞因子介导的疾病中的应用。
• Method of treating mucus hypersecretion
  申请人：Jung Birgit

  公开号：US20070123516A1

  公开（公告）日：2007-05-31

  The invention relates to the use of p38 kinase inhibitors for the preparation of a pharmaceutical composition suitable for inhalation for the treatment of mucus hypersecretion. Furthermore the invention is directed to pharmaceutical compositions suitable for inhalation comprising p38 kinase inhibitors and to methods for the preparation thereof.
• PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF RESPIRATORY AND GASTROINTESTINAL DISORDERS
  申请人：Jung Birgit

  公开号：US20090017036A1

  公开（公告）日：2009-01-15

  The present invention relates to novel pharmaceutical compositions comprising at least one EGFR kinase inhibitor and at least one additional active compound selected from beta-2 mimetics, steroids, PDE-IV inhibitors, p38 MAP kinase inhibitors, NK 1 antagonists and endothelin-antagonists, processes for preparing the compositions and the use thereof as medicament in the treatment of respiratory or gastrointestinal complaints, as well as inflammatory diseases of the joints, the skin or the eyes.
• Formulations with Improved Bioavailability
  申请人：Gereg, JR. George W.

  公开号：US20100016449A1

  公开（公告）日：2010-01-21

  Disclosed are solid oral formulations with improved dissolution and bioavailability for poorly water soluble pharmaceutical compounds.
• COMPOSITIONS AND METHODS FOR TREATMENT OF NEURODEGENERATIVE DISEASE
  申请人：Zack Donald Jeffrey

  公开号：US20110172206A1

  公开（公告）日：2011-07-14

  Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.