4-chloro-6-(4-methylpiperazin-1-yl)pyridin-2-amine | 959986-25-5

• 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-chloro-6-(4-methylpiperazin-1-yl)pyridin-2-amine
• 英文别名: 4-chloro-6-(4-methylpiperazin-1-yl)pyridine-2-amine
• CAS: 959986-25-5
• 化学式: C₁₀H₁₅ClN₄
• 分子量: 226.709
• InChiKey: RVZZSUIRMXPIOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-6-(4-methylpiperazin-1-yl)pyridin-2-amine 、 4-氰基苯硼酸 在 tris(dibenzylideneacetone)dipalladium (0) 、 potassium carbonate 、 tris[tert-butyl]phosphonium tetrafluoroborate 作用下， 以 异丙醇 为溶剂， 反应 16.0h， 以53%的产率得到4-[2-amino-6-(4-methylpiperazin-1-yl)pyridin-4-yl]-benzonitrile
  参考文献：
  名称：

  Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands

  摘要：

  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.

  DOI：

  10.1021/jm8005959
• 作为产物：
  描述：

  1-(4,6-dichloropyridin-2-yl)-4-methylpiperazine 在 tris-(dibenzylideneacetone)dipalladium(0) 二苯甲酮亚胺 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 、 盐酸羟胺 作用下， 以 甲苯 、 甲醇 为溶剂， 反应 15.0h， 以20%的产率得到4-chloro-6-(4-methylpiperazin-1-yl)pyridin-2-amine
  参考文献：
  名称：

  WO2007/141571

  摘要：

  公开号：

文献信息

• AMINOTHIAZOLE DERIVATIVES AS INHIBITORS OF MARK
  申请人：Bettati Michela

  公开号：US20100009987A1

  公开（公告）日：2010-01-14

  Compounds of formula (I): inhibit microtubule affinity regulating kinase (MARK) and therefore find use in treatment of neurodegenerative diseases associated with hyperphosphorylation of tau.

  化学式为（I）的化合物：抑制微管亲和力调节激酶（MARK），因此可用于治疗与tau过度磷酸化相关的神经退行性疾病。
• [EN] AMINOTHIAZOLE DERIVATIVES AS INHIBITORS OF MARK<br/>[FR] DÉRIVÉS D'AMINOTHIAZOLE EN TANT QU'INHIBITEURS DE MARK
  申请人：MERCK SHARP & DOHME

  公开号：WO2007141571A2

  公开（公告）日：2007-12-13

  [EN] Compounds of formula (I): inhibit microtubule affinity regulating kinase (MARK) and therefore find use in treatment of neurodegenerative diseases associated with hyperphosphorylation of tau.
  [FR] L'invention concerne des composés de formule (I) inhibant la kinase de régulation de l'affinité au microtubule (MARK) et qui, par conséquent, trouvent une utilisation dans le traitement de maladies neurodégénératives associées à l'hyperphosphorylation de tau.
• 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.
• WO2007/141571
  申请人：——

  公开号：——

  公开（公告）日：——