4-(tert-butyl)-6-chloro-2-(4-methylpiperazin-1-yl)pyrimidine | 1070214-65-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(tert-butyl)-6-chloro-2-(4-methylpiperazin-1-yl)pyrimidine
• 英文别名: 4-Tert-butyl-6-chloro-2-(4-methylpiperazin-1-yl)pyrimidine
• CAS: 1070214-65-1
• 化学式: C₁₃H₂₁ClN₄
• mdl: MFCD13324055
• 分子量: 268.79
• InChiKey: JBHPFWNFKKHEJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.692
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(tert-butyl)-6-chloro-2-(4-methylpiperazin-1-yl)pyrimidine 、 {(1S,4R)-4-[3-((S)-1,2-dimethylpyrrolidin-2-yl)[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl}urea 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以20%的产率得到1-(6-(tert-butyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3-((1S,4R)-4-((3-((S)-1,2-dimethylpyrrolidin-2-yl)[1,2,4]triazolo[4,3-a]pyridin-6-yl)oxy)-1,2,3,4-tetrahydronaphthalen-1-yl)urea
  参考文献：
  名称：

  [EN] (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL) UREIDO DERIVATIVES AS ANTI-INFLAMMATORY P38 MAPK INHIBITORS FOR TREATING DISEASES OF THE RESPIRATORY TRACT
  [FR] DÉRIVÉS DE (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TÉTRAHYDRONAPHTALÉN-1-YL)URÉIDO EN TANT QU'INHIBITEURS DE P38 MAPK ANTI-INFLAMMATOIRES POUR TRAITER DES MALADIES DU TRACTUS RESPIRATOIRE

  摘要：

  本发明涉及(4-(([1,2,4]三唑[4,3-a]吡啶-6-基)氧基)-1,2,3,4-四氢萘-1-基)脲衍生物，该衍生物作为抗炎剂用于治疗呼吸道的疾病，是p38 MAPK（丝裂原活化蛋白激酶）的抑制剂。

  公开号：

  WO2018224423A1
• 作为产物：
  描述：

  特戊酰基乙酸乙酯 在 potassium tert-butylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 4-(tert-butyl)-6-chloro-2-(4-methylpiperazin-1-yl)pyrimidine
  参考文献：
  名称：

  [EN] (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL) UREIDO DERIVATIVES AS ANTI-INFLAMMATORY P38 MAPK INHIBITORS FOR TREATING DISEASES OF THE RESPIRATORY TRACT
  [FR] DÉRIVÉS DE (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TÉTRAHYDRONAPHTALÉN-1-YL)URÉIDO EN TANT QU'INHIBITEURS DE P38 MAPK ANTI-INFLAMMATOIRES POUR TRAITER DES MALADIES DU TRACTUS RESPIRATOIRE

  摘要：

  本发明涉及(4-(([1,2,4]三唑[4,3-a]吡啶-6-基)氧基)-1,2,3,4-四氢萘-1-基)脲衍生物，该衍生物作为抗炎剂用于治疗呼吸道的疾病，是p38 MAPK（丝裂原活化蛋白激酶）的抑制剂。

  公开号：

  WO2018224423A1

文献信息

• Kinase inhibitors
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US10364245B2

  公开（公告）日：2019-07-30

  Compounds of formula (I) defined herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.

  本文定义的式 (I) 化合物是 p38 MAPK 抑制剂，可用作治疗呼吸道疾病等的抗炎剂。
• Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands
  作者：Robert J. Altenbach、Ronald M. Adair、Brian M. Bettencourt、Lawrence A. Black、Shannon R. Fix-Stenzel、Sujatha M. Gopalakrishnan、Gin C. Hsieh、Huaqing Liu、Kennan C. Marsh、Michael J. McPherson、Ivan Milicic、Thomas R. Miller、Timothy A. Vortherms、Usha Warrior、Jill M. Wetter、Neil Wishart、David G. Witte、Prisca Honore、Timothy A. Esbenshade、Arthur A. Hancock、Jorge D. Brioni、Marlon D. Cowart

  DOI：10.1021/jm8005959

  日期：2008.10.23

  A series of 2-aminopyrimidines was synthesized as ligands of the histamine H-4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4, 4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.
• (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL) UREIDO DERIVATIVES AS ANTI-INFLAMMATORY P38 MAPK INHIBITORS FOR TREATING DISEASES OF THE RESPIRATORY TRACT
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：EP3634961A1

  公开（公告）日：2020-04-15
• (4-(([1,2,4]TRIAZOLO[4,3-A]PYRIDINE-6-YL)OXY)-1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL)UREIDO DERIVATIVES AS ANTI-INFLAMMATORY P38 MAPK INHIBITORS FOR TREATING DISEASES OF THE RESPIRATORY TRACT
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：EP3634961B1

  公开（公告）日：2021-05-26
• KINASE INHIBITORS
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US20180354945A1

  公开（公告）日：2018-12-13

  Compounds of formula (I) defined herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.