5-tert-butyl-N-methyl-2-phenylpyrazol-3-amine | 443912-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-tert-butyl-N-methyl-2-phenylpyrazol-3-amine
• CAS: 443912-86-5
• 化学式: C₁₄H₁₉N₃
• 分子量: 229.325
• InChiKey: VQLZLHSHQOBGQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 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：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  对氯苯异氰酸酯 、 5-tert-butyl-N-methyl-2-phenylpyrazol-3-amine 以 二氯甲烷 为溶剂， 反应 48.0h， 以0.16 g的产率得到1-(5-Tert-butyl-2-phenylpyrazol-3-yl)-3-(4-chlorophenyl)-1-methylurea
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r
• 作为产物：
  描述：

  N-(5-tert-butyl-2-phenylpyrazol-3-yl)formamide 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 5-tert-butyl-N-methyl-2-phenylpyrazol-3-amine
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r

文献信息

• BICYCLIC AMIDES AS KINASE INHIBITORS
  申请人：Bold Guido

  公开号：US20110301157A1

  公开（公告）日：2011-12-08

  The invention relates to compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.
• [EN] TARGETED NEK7 INHIBITION FOR MODULATION OF THE NLRP3 INFLAMMASOME<br/>[FR] INHIBITION CIBLÉE DE NEK7 POUR LA MODULATION DE L'INFLAMMASOME NLRP3
  申请人：HALIA THERAPEUTICS INC

  公开号：WO2021226547A2

  公开（公告）日：2021-11-11

  Compositions comprising at least one NEK7 protein and a NEK7 small molecule inhibitor compound comprising at least one of the following features: (i) a hinge-binding element comprising at least one hydrogen donor and at least one hydrogen acceptor, (ii) a flexible linker, (iii) a urea linker, or (iv) a hydrophobic back pocket group. Methods associated with preparation and use of such NEK7 inhibitors, pharmaceutical compositions comprising such NEK7 inhibitors and methods to prevent diseases or disorders (e.g., via modulation of NLRP3 inflammasome activity) are also provided.
• Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate
  作者：John Regan、Steffen Breitfelder、Pier Cirillo、Thomas Gilmore、Anne G. Graham、Eugene Hickey、Bernhard Klaus、Jeffrey Madwed、Monica Moriak、Neil Moss、Chris Pargellis、Sue Pav、Alfred Proto、Alan Swinamer、Liang Tong、Carol Torcellini

  DOI：10.1021/jm020057r

  日期：2002.7.1

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.