6,7-Dihydro-4H-pyrazolo[5,1-C][1,4]oxazin-3-amine | 1785362-30-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6,7-Dihydro-4H-pyrazolo[5,1-C][1,4]oxazin-3-amine
• CAS: 1785362-30-2
• 化学式: C₆H₉N₃O
• 分子量: 139.157
• InChiKey: NXZCEONGJPCYGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-N-甲基-5-(三氟甲基)嘧啶-4-胺 、 6,7-Dihydro-4H-pyrazolo[5,1-C][1,4]oxazin-3-amine 在 叔丁醇 作用下， 反应 0.25h， 生成 N2-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-3-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

  摘要：

  Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the neuroscience research community because it is one of the most compelling targets for a potential disease-modifying Parkinson's disease therapy. Herein, we disclose structurally diverse small molecule inhibitors suitable for assessing the implications of sustained in vivo LARK2 inhibition. Using previously reported aminopyrazole 2 as a lead molecule, we were able to engineer structural modifications in the solvent-exposed region of the ATP-binding site that significantly improve human hepatocyte stability, rat free brain exposure, and CYP inhibition and induction liabilities. Disciplined application of established optimal CNS design parameters culminated in the rapid identification of GNE-0877 (11) and GNE-9605 (20) as highly potent and selective LRRK2 inhibitors. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies.

  DOI：

  10.1021/jm401654j
• 作为产物：
  描述：

  3-(2-Hydroxyethoxymethyl)pyrazole 在 硫酸 、 硝酸 、 铁粉 、 氯化铵 、 氰基亚甲基三正丁基膦 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 65.5h， 生成 6,7-Dihydro-4H-pyrazolo[5,1-C][1,4]oxazin-3-amine
  参考文献：
  名称：

  [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK

  摘要：

  融合的芳香族双环取代5-(2-氨基-4-嘧啶基)-氰基吲哚衍生物（I）用于哺乳动物的治疗和/或预防，特别是用于抑制NF-KB诱导激酶（NIK - 也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。

  公开号：

  WO2018002219A1

文献信息

• Cyanoindoline derivatives as NIK inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US11186589B2

  公开（公告）日：2021-11-30

  The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及可用于哺乳动物治疗和/或预防的药物制剂，尤其涉及可用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病等疾病的NF-κB诱导激酶（NIK-又称MAP3K14）抑制剂。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物或药物组合物预防或治疗癌症、炎症性疾病、代谢紊乱（包括肥胖和糖尿病）和自身免疫性疾病等疾病。
• CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP3478673B1

  公开（公告）日：2020-09-16