tert-butyl 4-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-ethyl] 5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate | 1426700-03-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-ethyl] 5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate
• 英文别名: tert-Butyl 4-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-ethyl]-5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate；tert-butyl 4-[3-[1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl]piperidine-1-carboxylate
• CAS: 1426700-03-9
• 化学式: C₂₆H₃₅ClN₆O₃
• 分子量: 515.055
• InChiKey: DCHNAKQDSWICIY-UHFFFAOYSA-N

物化性质

• 沸点：
  664.7±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-ethyl] 5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 7.17h， 生成 1-{1-[5-chloro-2-methoxy-4-methyl-3-(1-methylpiperidin-4-yl)phenyl]ethyl}-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ)

  摘要：

  A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3K delta) led to the discovery of clinical candidate INCB050465 (20, parsaclisib). The unique structure of 20 contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in other PI3K delta inhibitors, such as idelalisib (1), duvelisib (2), and INCB040093 (3, dezapelisib). Parsaclisib (20) is a potent and highly selective inhibitor of PI3K delta with drug-like ADME properties that exhibited an excellent in vivo profile as demonstrated through pharmacokinetic studies in rats, dogs, and monkeys and through pharmacodynamic and efficacy studies in a mouse Pfeiffer xenograft model.

  DOI：

  10.1021/acsmedchemlett.9b00334
• 作为产物：
  描述：

  tert-butyl 4-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]piperidine-1-carboxylate 、 3-甲基-1H-吡唑并[3,4-D]嘧啶-4-胺 生成 tert-butyl 4-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-ethyl] 5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate
  参考文献：
  名称：

  HETEROCYCLYLAMINES AS PI3K INHIBITORS

  摘要：

  本发明提供了式I的杂环胺衍生物：其中变量在此定义，其调节磷脂酰肌醇3激酶（PI3Ks）的活性，并且在治疗与PI3Ks活性相关的疾病方面有用，包括例如炎症性疾病、免疫性疾病、癌症和其他疾病。

  公开号：

  US20160022685A1

文献信息

• USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K-DELTA RELATED DISORDERS
  申请人：Incyte Corporation

  公开号：US20140249132A1

  公开（公告）日：2014-09-04

  The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.

  本申请提供了使用以下化合物治疗PI3Kδ相关疾病的方法： 或其药用盐的方法。
• HETEROCYCLYLAMINES AS PI3K INHIBITORS
  申请人：Li Yun-Long

  公开号：US20130059835A1

  公开（公告）日：2013-03-07

  The present invention provides heterocyclylamine derivatives of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

  本发明提供了式I的杂环胺衍生物： 其中变量如本文所定义，调节磷脂酰肌醇3-激酶（PI3Ks）的活性，并且在治疗与PI3Ks活性相关的疾病方面具有用处，例如炎症性疾病、免疫性疾病、癌症和其他疾病。
• Heterocyclylamines as PI3K inhibitors
  申请人：Li Yun-Long

  公开号：US09199982B2

  公开（公告）日：2015-12-01

  The present invention provides heterocyclylamine derivatives of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

  本发明提供了式I的杂环胺衍生物：其中变量在此定义，可调节磷脂酰肌醇3-激酶（PI3Ks）的活性，并且在治疗与PI3Ks活性相关的疾病方面有用，包括例如炎症性疾病，免疫性疾病，癌症和其他疾病。
• USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K RELATED DISORDERS
  申请人：Incyte Holdings Corporation

  公开号：EP3632442A1

  公开（公告）日：2020-04-08

  The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.

  本申请提供了使用式 I 化合物治疗 PI3Kδ 相关疾病的方法： 或其药学上可接受的盐。
• USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K-DELTA RELATED DISORDERS
  申请人：Incyte Corporation

  公开号：US20190040067A1

  公开（公告）日：2019-02-07

  The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.