tert-butyl (3S)-3-{[9-ethyl-8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]amino}pyrrolidine-1-carboxylate | 1610703-84-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: tert-butyl (3S)-3-{[9-ethyl-8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]amino}pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3S)-3-[[9-ethyl-8-(1-ethyl-5-methylpyrazol-4-yl)purin-6-yl]amino]pyrrolidine-1-carboxylate
• CAS: 1610703-84-8
• 化学式: C₂₂H₃₂N₈O₂
• 分子量: 440.548
• InChiKey: ZJKWXMLXSVEVEZ-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-3-{[9-ethyl-8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]amino}pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  Projected Dose Optimization of Amino- and Hydroxypyrrolidine Purine PI3Kδ Immunomodulators

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c00237
• 作为产物：
  描述：

  1-乙基-5-甲基-1H-吡唑-4-甲醛 在 iron(III) chloride hexahydrate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 86.0h， 生成 tert-butyl (3S)-3-{[9-ethyl-8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9H-purin-6-yl]amino}pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Projected Dose Optimization of Amino- and Hydroxypyrrolidine Purine PI3Kδ Immunomodulators

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c00237

文献信息

• [EN] PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA<br/>[FR] INHIBITEURS PURIQUES DE LA PHOSPHATIDYLINOSITOL 3-KINASE DELTA HUMAINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2014075393A1

  公开（公告）日：2014-05-22

  The instant invention provides compounds of formula I which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.

  该即时发明提供了式I的化合物，这些化合物是PI3K-δ抑制剂，因此可用于治疗PI3K-δ介导的疾病，如炎症、哮喘、慢性阻塞性肺病和癌症。
• PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20160207926A1

  公开（公告）日：2016-07-21

  The instant invention provides compounds of formula I which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.

  本发明提供了I式化合物，它们是PI3K-delta抑制剂，因此可用于治疗PI3K-delta介导的疾病，如炎症、哮喘、COPD和癌症。
• Evaluation of WO2014075392 and WO2014075393, Merck’s first PI3Kδ inhibitor filings
  作者：Peter Norman

  DOI：10.1517/13543776.2014.969710

  日期：2014.11

  Introduction: There is considerable interest in the development of selective PI3K inhibitors for the treatment of inflammatory diseases and haematological cancers. Merck has no previous filings in this field but licensed Exelixis' programme, including its lead compound XL-499, in December 2011.Areas covered: Both applications claim novel 9-alkyl-6,8-disubstituted purine derivatives as selective delta inhibitors for the treatment of asthma, obstructive airways disease, arthritis and cancer. The two applications differ in the range of exemplified substituents, the first focusing on 8-heteroaryl substituted purines, the second on 8-aminopurine derivatives. Many of the exemplified compounds have IC50 values < 10 nM against PI3K delta with a number having sub-nanomolar potency.Expert Opinion: The compounds appear to be XL-499 derivatives, some of which are more potent than XL-499. The compounds claimed by Merck are some of the most potent PI3K inhibitors yet described but it is unclear whether a development compound has been identified.
• US9938281B2
  申请人：——

  公开号：US9938281B2

  公开（公告）日：2018-04-10
• Projected Dose Optimization of Amino- and Hydroxypyrrolidine Purine PI3Kδ Immunomodulators
  作者：Joey L. Methot、Hua Zhou、Meredeth A. McGowan、Neville John Anthony、Matthew Christopher、Yudith Garcia、Abdelghani Achab、Kathryn Lipford、Benjamin Wesley Trotter、Michael D. Altman、Xavier Fradera、Charles A. Lesburg、Chaomin Li、Stephen Alves、Craig P. Chappell、Renu Jain、Ruban Mangado、Elaine Pinheiro、Sybill M. G. Williams、Peter Goldenblatt、Armetta Hill、Lynsey Shaffer、Dapeng Chen、Vincent Tong、Robbie L. McLeod、Hyun-Hee Lee、Hongshi Yu、Sanjiv Shah、Jason D. Katz

  DOI：10.1021/acs.jmedchem.1c00237

  日期：2021.4.22