tert-butyl 4-(2-chloroquinazolin-4-yl)piperazine-1-carboxylate | 950666-26-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(2-chloroquinazolin-4-yl)piperazine-1-carboxylate
• 英文别名: 2-chloro-4-(4-Boc-piperazin-1-yl)quinazoline；t-butyl 4-(2-chloroquinazolin-4-yl)piperazine-1-carboxylate
• CAS: 950666-26-9
• 化学式: C₁₇H₂₁ClN₄O₂
• 分子量: 348.832
• InChiKey: ZBSOMMYUMAVBCI-UHFFFAOYSA-N

物化性质

• 沸点：
  467.4±45.0 °C(Predicted)
• 密度：
  1.280±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-chloroquinazolin-4-yl)piperazine-1-carboxylate 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 4-(piperazin-1-yl)-2-(thiophen-2-yl)quinazoline
  参考文献：
  名称：

  Evaluation of Quinazoline Analogues as Glucocerebrosidase Inhibitors with Chaperone Activity

  摘要：

  Gaucher disease is a lysosomal storage disorder (LSD) caused by deficiency in the enzyme glucocerebrosidase (GC). Small molecule chaperones of protein folding and translocation have been proposed as a promising therapeutic approach to this LSD. Most small molecule chaperones described in the literature contain an iminosugar scaffold. Here we present the discovery and evaluation of a new series of GC inhibitors with a quinazoline core. We demonstrate that this series can improve the translocation of GC to the lysosome in patient-derived cells. To optimize this chemical series, systematic synthetic modifications were performed and the SAR was evaluated and compared using three different readouts of compound activity: enzymatic inhibition, enzyme thermostabilization, and lysosomal translocation of GC.

  DOI：

  10.1021/jm1008902
• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 反应 11.0h， 生成 tert-butyl 4-(2-chloroquinazolin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis and evaluation of quinazoline derivatives as Gαq/11 proteins inhibitors against uveal melanoma

  摘要：

  DOI：

  10.1016/j.bioorg.2023.107005

文献信息

• AMINOPYRROLIDINE COMPOUND
  申请人：Okubo Taketoshi

  公开号：US20090291940A1

  公开（公告）日：2009-11-26

  Disclosed is an aminopyrrolidine compound represented by the formula [I] or a pharmaceutically acceptable salt thereof. The compound or the salt is useful as a prophylactic/therapeutic agent for mode disorder such as depression, anxiety disorder, anorexia, cachexia, pain and drug dependence, whose action relies on the MC 4 receptor antagonistic effect.

  本发明公开了一种氨基吡咯烷化合物，其化学式为[I]，或其药学上可接受的盐。该化合物或其盐可用作预防/治疗药物，针对情绪障碍，如抑郁症、焦虑症、厌食症、消瘦症、疼痛和药物依赖等，其作用依赖于MC4受体拮抗作用。
• Aminopyrrolidine compound
  申请人：Taisho Pharmaceutical Co., Ltd

  公开号：US08044068B2

  公开（公告）日：2011-10-25

  Disclosed is an aminopyrrolidine compound represented by the formula [I] or a pharmaceutically acceptable salt thereof. The compound or the salt is useful as a prophylactic/therapeutic agent for mode disorder such as depression, anxiety disorder, anorexia, cachexia, pain and drug dependence, whose action relies on the MC4 receptor antagonistic effect.

  公开了一种由公式[I]表示的氨基吡咯烷化合物或其药学上可接受的盐。该化合物或盐可用作预防/治疗剂，用于模式失调，如抑郁症、焦虑症、厌食症、消瘦症、疼痛和药物依赖症，其作用依赖于MC4受体拮抗作用。
• EP2003131
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery and rational design of 2-aminopyrimidine-based derivatives targeting Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3)
  作者：Yingxiu Li、Peng Wang、Cong Chen、Tianyu Ye、Yufei Han、Yunlei Hou、Yajing Liu、Ping Gong、Mingze Qin、Yanfang Zhao

  DOI：10.1016/j.bioorg.2020.104361

  日期：2020.11

  Herein, with the help of computer-aided drug design (CADD), we describe the structure-based rational drug design, structure-activity relationships, and synthesis of a series of 2-aminopyrimidine derivatives that inhibit both JAK2 and FLT3 kinases. These screening cascades revealed that compound 14l demonstrated the most inhibitory activity with IC₅₀ values of 1.8 and 0.68 nM against JAK2 and FLT3 respectively. 14l also showed potent anti-proliferative activities against HEL (IC₅₀ = 0.84 μM) and Molm-13 (IC₅₀ = 0.019 μM) cell lines, but relatively weak cytotoxicity against K562 and PC-3 cell lines, which proved that it might have high target specificity. In vitro metabolism assay, 14l exhibited moderate stability in RLM (Rat Liver Microsomes) with a half-life time of 31 min. In the cellular context of Molm-13, 14l induced cell cycle arrest in G₁/S phase and enhanced apoptosis in a dose-dependent manner. These results indicate that 14l is a promising dual JAK2/FLT3 inhibitor and worthy of further development.
• WO2007/108744
  申请人：——

  公开号：——

  公开（公告）日：——