2-chloro-N-(1-methyl-1H-imidazol-4-yl)quinazolin-4-amine | 1220518-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-chloro-N-(1-methyl-1H-imidazol-4-yl)quinazolin-4-amine
• 英文别名: 2-chloro-N-(1-methylimidazol-4-yl)quinazolin-4-amine
• CAS: 1220518-16-0
• 化学式: C₁₂H₁₀ClN₅
• 分子量: 259.698
• InChiKey: WOGFUSAHSVIDDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(1-methyl-1H-imidazol-4-yl)quinazolin-4-amine 、 (S)-(-)- α-甲基苄胺 以 N-甲基吡咯烷酮 为溶剂， 反应 4.0h， 以18%的产率得到(S)-N4-(1-methyl-1H-imidazol-4-yl)-N2-(1-phenylethyl)quinazoline2,4-diamine
  参考文献：
  名称：

  [EN] IMIDAZOLE-CONTAINING INHIBITORS OF ALK2 KINASE
  [FR] INHIBITEURS DE LA KINASE ALK2 CONTENANT DE L'IMIDAZOLE

  摘要：

  揭示了化合物的公式（I）、（II）、（III）和（IV），以及它们的药用盐。这些化合物是ALK2激酶的抑制剂。还提供了包含公式（I）、（II）、（III）或（IV）的化合物或其药用盐的药物组合物，以及涉及使用这些化合物或其药用盐和组合物治疗和预防各种疾病和病况的方法，如纤维性骨化进行性疾病。

  公开号：

  WO2018232094A1
• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 N,N-二甲基苯胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 2-chloro-N-(1-methyl-1H-imidazol-4-yl)quinazolin-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。
• IMIDAZOLE-CONTAINING INHIBITORS OF ALK2 KINASE
  申请人：Biocryst Pharmaceuticals, Inc.

  公开号：EP3638229A1

  公开（公告）日：2020-04-22
• [EN] IMIDAZOLE-CONTAINING INHIBITORS OF ALK2 KINASE<br/>[FR] INHIBITEURS DE LA KINASE ALK2 CONTENANT DE L'IMIDAZOLE
  申请人：BIOCRYST PHARM INC

  公开号：WO2018232094A1

  公开（公告）日：2018-12-20

  Disclosed are compounds of formula (I), (II), (III), and (IV), and pharmaceutically acceptable salts thereof. The compounds are inhibitors of ALK2 kinase. Also provided are pharmaceutical compositions comprising a compound of formula (I), (II), (III), or (IV), or pharmaceutically acceptable salt thereof, and methods involving use of the compounds or pharmaceutically acceptable salts thereof and compositions in the treatment and prevention of various diseases and conditions, such as fibrodysplasia ossificans progressiva.

  揭示了化合物的公式（I）、（II）、（III）和（IV），以及它们的药用盐。这些化合物是ALK2激酶的抑制剂。还提供了包含公式（I）、（II）、（III）或（IV）的化合物或其药用盐的药物组合物，以及涉及使用这些化合物或其药用盐和组合物治疗和预防各种疾病和病况的方法，如纤维性骨化进行性疾病。
• 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.