(S)-(3-aminopyrrolidin-1-yl)(cyclopropyl)methanone | 1286317-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-(3-aminopyrrolidin-1-yl)(cyclopropyl)methanone
• 英文别名: [(3S)-3-aminopyrrolidin-1-yl]-cyclopropylmethanone
• CAS: 1286317-23-4
• 化学式: C₈H₁₄N₂O
• 分子量: 154.212
• InChiKey: QTYGXDUXIZLHGI-ZETCQYMHSA-N

物化性质

• 沸点：
  304.5±35.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-9-ethyl-8-(6-(trifluoromethyl)pyridin-3-yl)-9H-purine 、 (S)-(3-aminopyrrolidin-1-yl)(cyclopropyl)methanone 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以37%的产率得到N-[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]-9-ethyl-8-[6-(trifluoromethyl)pyridin-3-yl]-9H-purin-6-amine
  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。
• Discovery of 1-Pyrimidinyl-2-Aryl-4,6-Dihydropyrrolo [3,4-d]Imidazole-5(1H)-Carboxamide as a Novel JNK Inhibitor
  作者：Miyoung Jang、Youri Oh、Hyunwook Cho、Songyi Yang、Hyungwoo Moon、Daseul Im、Jung-Mi Hah

  DOI：10.3390/ijms21051698

  日期：——

  We designed and synthesized 1-pyrimidinyl-2-aryl-4, 6-dihydropyrrolo [3,4-d] imidazole-5(1H)-carboxamide derivatives as selective inhibitors of c-Jun-N-terminal Kinase 3 (JNK3), a target for the treatment of neurodegenerative diseases. Based on the compounds found in previous studies, a novel scaffold was designed to improve pharmacokinetic characters and activity, and compound 18a, (R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydro pyrrolo [3,4-d]imidazole-5(1H)-carboxamide, showed the highest IC50 value of 2.69 nM. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases, having mild activity against JNK2, RIPK3, and GSK3β, which also known to involve in neuronal apoptosis.

  我们设计并合成了1-嘧啶基-2-芳基-4,6-二氢吡咯[3,4-d]咪唑-5(1H)-甲酰胺衍生物，作为选择性抑制剂针对c-Jun-N-末端激酶3 (JNK3)，这是治疗神经退行性疾病的靶点。基于先前研究中发现的化合物，设计了一种新颖的支架以改善药代动力学特性和活性，其中化合物18a，(R)-1-(2-((1-(环丙酰)吡咯烷-3-基)氨基)嘧啶-4-基)-2-(3,4-二氯苯基)-4,6-二氢吡咯[3,4-d]咪唑-5(1H)-甲酰胺，显示了最高的IC50值为2.69 nM。激酶分析结果还显示在38种激酶中对JNK3具有高度选择性，对JNK2、RIPK3和GSK3β具有轻微活性，这些激酶也已知参与神经细胞凋亡。
• 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。
• Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1<i>H-</i>pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
  作者：Youri Oh、Miyoung Jang、Hyunwook Cho、Songyi Yang、Daseul Im、Hyungwoo Moon、Jung-Mi Hah

  DOI：10.1080/14756366.2019.1705294

  日期：2020.1.1

  3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC₅₀ value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.
• US8445501B2
  申请人：——

  公开号：US8445501B2

  公开（公告）日：2013-05-21