2-(5-amino-1-p-tolyl-1H-pyrazol-3-yl)-2-methylpropan-1-ol | 489432-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(5-amino-1-p-tolyl-1H-pyrazol-3-yl)-2-methylpropan-1-ol
• 英文别名: 2-[5-amino-1-(4-methylphenyl)pyrazol-3-yl]-2-methylpropan-1-ol
• CAS: 489432-34-0
• 化学式: C₁₄H₁₉N₃O
• 分子量: 245.324
• InChiKey: XBKFIUGZCJHHOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-amino-1-p-tolyl-1H-pyrazol-3-yl)-2-methylpropan-1-ol 、 氯甲酸-2,2,2-三氯乙酯 在 sodium hydroxide 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 2,2,2-trichloroethyl 3-(2-hydroxy-1,1-dimethylethyl)-1-p-tolyl-1H-pyrazol-5-ylcarbamate
  参考文献：
  名称：

  [EN] PYRAZOLE UREA DERIVATIVES USED AS KINASE INHIBITORS
  [FR] DÉRIVÉS DE PYRAZOLE URÉE UTILISÉS COMME INHIBITEURS DE KINASE

  摘要：

  公开号：

  WO2009015000A8
• 作为产物：
  描述：

  羟基三甲基乙酸甲酯 在 咪唑 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.0h， 生成 2-(5-amino-1-p-tolyl-1H-pyrazol-3-yl)-2-methylpropan-1-ol
  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

• Pyrazole urea derivatives used as kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US08202899B2

  公开（公告）日：2012-06-19

  Compounds of Formula (I) where R1 and R2 are as defined herein, and pharmaceutically acceptable salts thereof, are useful in the treatment and prevention of various disorders mediated by kinases.

  式(I)中R1和R2所定义的化合物及其药学上可接受的盐，可用于治疗和预防由激酶介导的各种疾病。
• PYRAZOLE UREA DERIVATIVES USED AS KINASE INHIBITORS
  申请人：Munson Mark C.

  公开号：US20100331385A1

  公开（公告）日：2010-12-30

  Compounds of Formula (I) where R 1 and R 2 are as defined herein, and pharmaceutically acceptable salts thereof, are useful in the treatment and prevention of various disorders mediated by kinases

  公式（I）中，其中R1和R2如定义所述的化合物及其药学上可接受的盐，可用于治疗和预防由激酶介导的各种疾病。
• US8202899B2
  申请人：——

  公开号：US8202899B2

  公开（公告）日：2012-06-19