2-chloro-N-(1-methyl-1H-imidazol-4-yl)-5-[(4-methylphenyl)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine | 1220517-78-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(1-methyl-1H-imidazol-4-yl)-5-[(4-methylphenyl)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine
• 英文别名: 2-chloro-N-(1-methylimidazol-4-yl)-5-(4-methylphenyl)sulfonylpyrrolo[3,2-d]pyrimidin-4-amine
• CAS: 1220517-78-1
• 化学式: C₁₇H₁₅ClN₆O₂S
• 分子量: 402.864
• InChiKey: LYPCUNKEZKYOET-UHFFFAOYSA-N

物化性质

• 沸点：
  622.8±65.0 °C(predicted)
• 密度：
  1.54±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(1-methyl-1H-imidazol-4-yl)-5-[(4-methylphenyl)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine 在 水 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 正丁醇 为溶剂， 反应 3.0h， 生成 N²-[1-(5-fluoropyrimidin-2-yl)ethyl]-N⁴-(1-methyl-1H-imidazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors

  摘要：

  Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.

  DOI：

  10.1021/jm401546n
• 作为产物：
  描述：

  对甲苯磺酰氯 在 四丁基硫酸氢铵 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.5h， 生成 2-chloro-N-(1-methyl-1H-imidazol-4-yl)-5-[(4-methylphenyl)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors

  摘要：

  Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.

  DOI：

  10.1021/jm401546n

文献信息

• [EN] HETEROCYCLIC JAK KINASE INHIBITORS<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA KINASE JAK
  申请人：ASTRAZENECA AB

  公开号：WO2010038060A1

  公开（公告）日：2010-04-08

  The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.

  本发明涉及式（I）化合物及其盐、药物组合物、使用方法和制备方法。这些化合物可用于治疗骨髓增生性疾病和癌症。
• HETEROCYCLIC JAK KINASE INHIBITORS
  申请人：Chuaqui Claudio Edmundo

  公开号：US20110201628A1

  公开（公告）日：2011-08-18

  The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.

  本发明涉及公式（I）的化合物及其盐，制药组合物，使用方法和制备方法。这些化合物提供了治疗骨髓增生性疾病和癌症的方法。
• Discovery of 1-Methyl-1<i>H</i>-imidazole Derivatives as Potent Jak2 Inhibitors
  作者：Qibin Su、Stephanos Ioannidis、Claudio Chuaqui、Lynsie Almeida、Marat Alimzhanov、Geraldine Bebernitz、Kirsten Bell、Michael Block、Tina Howard、Shan Huang、Dennis Huszar、Jon A. Read、Caroline Rivard Costa、Jie Shi、Mei Su、Minwei Ye、Michael Zinda

  DOI：10.1021/jm401546n

  日期：2014.1.9

  Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.