(S)-tert-butyl (1-(4-aminopyridin-3-yl)piperidin-3-yl)carbamate | 1405128-57-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-tert-butyl (1-(4-aminopyridin-3-yl)piperidin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3S)-1-(4-aminopyridin-3-yl)piperidin-3-yl]carbamate
• CAS: 1405128-57-5
• 化学式: C₁₅H₂₄N₄O₂
• 分子量: 292.381
• InChiKey: UNWYFQZCUJVMMO-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl (1-(4-aminopyridin-3-yl)piperidin-3-yl)carbamate 在 三甲基膦 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors

  摘要：

  High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0.024 nM and 0.095 nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50 = 28 nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.09.067
• 作为产物：
  描述：

  3-氟-4-硝基吡啶 在 palladium 10% on activated carbon 氢气 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 16.0h， 生成 (S)-tert-butyl (1-(4-aminopyridin-3-yl)piperidin-3-yl)carbamate
  参考文献：
  名称：

  [EN] BICYCLIC PYRIDAZINE COMPOUNDS AS PIM INHIBITORS
  [FR] COMPOSÉS PYRIDAZINES BICYCLIQUES EN TANT QU'INHIBITEURS DE PIM

  摘要：

  该发明涉及公式I和I'的双环化合物及其盐。在某些实施例中，该发明涉及Pim-1和/或Pim-2以及/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文披露的化合物的药物组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症中的应用。

  公开号：

  WO2012148775A1

文献信息

• Bicyclic Pyridazine Compounds as PIM Inhibitors
  申请人：D'amico Derin C.

  公开号：US20140221344A1

  公开（公告）日：2014-08-07

  The invention relates to bicyclic compounds of formulas I and I′, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

  本发明涉及式I和I'的双环化合物及其盐。在某些实施例中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，本发明涉及包含所述化合物的制药组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症方面的应用。
• 신규한 PIM 키나아제 억제 화합물 및 이의 용도
  申请人：제일약품주식회사

  公开号：KR20230154382A

  公开（公告）日：2023-11-08

  본 발명은 신규한 PIM 키나아제 억제제 및 이의 용도에 관한 것으로, 보다 상세하게는 PIM 키나아제 억제 활성을 가지는 신규한 화합물 및 이를 포함하는 PIM 키나아제 활성과 관련된 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다. 본 발명의 화합물은 심장독성이 낮으면서도, 효과적으로 PIM 키나아제 억제 활성을 가지는 것을 확인하였으므로, 본 발명의 화합물은 PIM 키나아제 활성과 관련된 암, 자가면역질환, 골수 증식성 장애 또는 죽상동맥경화증과 같은 다양한 질환의 예방, 개선 또는 치료용 조성물로 유용하게 사용될 수 있다.

  本发明涉及新型PIM激酶抑制剂及其用途，更具体地说，涉及具有PIM激酶抑制活性的新型化合物和包含这些化合物的预防、改善或治疗与PIM激酶活性相关疾病的组合物。由于已发现本发明化合物具有有效的 PIM 激酶抑制活性，且心脏毒性低，因此本发明化合物可用于预防、改善或治疗与 PIM 激酶活性相关的各种疾病（如癌症、自身免疫性疾病、骨髓增生性疾病或动脉粥样硬化）的组合物中。
• US9187486B2
  申请人：——

  公开号：US9187486B2

  公开（公告）日：2015-11-17
• Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors
  作者：Ryan P. Wurz、Christine Sastri、Derin C. D’Amico、Brad Herberich、Claire L.M. Jackson、Liping H. Pettus、Andrew S. Tasker、Bin Wu、Nadia Guerrero、J. Russell Lipford、Jeffrey T. Winston、Yajing Yang、Paul Wang、Yen Nguyen、Kristin L. Andrews、Xin Huang、Matthew R. Lee、Christopher Mohr、J.D. Zhang、Darren L. Reid、Yang Xu、Yihong Zhou、Hui-Ling Wang

  DOI：10.1016/j.bmcl.2016.09.067

  日期：2016.11

  High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0.024 nM and 0.095 nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50 = 28 nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication. (C) 2016 Elsevier Ltd. All rights reserved.
• [EN] BICYCLIC PYRIDAZINE COMPOUNDS AS PIM INHIBITORS<br/>[FR] COMPOSÉS PYRIDAZINES BICYCLIQUES EN TANT QU'INHIBITEURS DE PIM
  申请人：AMGEN INC

  公开号：WO2012148775A1

  公开（公告）日：2012-11-01

  The invention relates to bicyclic compounds of formulas I and I', and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

  该发明涉及公式I和I'的双环化合物及其盐。在某些实施例中，该发明涉及Pim-1和/或Pim-2以及/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文披露的化合物的药物组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症中的应用。