tert-butyl ((3S)-1-(4-nitro-5-isothiazolyl)-3-piperidinyl)carbamate | 1405127-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl ((3S)-1-(4-nitro-5-isothiazolyl)-3-piperidinyl)carbamate
• 英文别名: tert-butyl N-[(3S)-1-(4-nitro-1,2-thiazol-5-yl)piperidin-3-yl]carbamate
• CAS: 1405127-91-4
• 化学式: C₁₃H₂₀N₄O₄S
• 分子量: 328.392
• InChiKey: WTGULFGSWLBMPO-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl ((3S)-1-(4-nitro-5-isothiazolyl)-3-piperidinyl)carbamate 在 indium 、 sodium azide 、 硫酸 、 氯化铵 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 2.67h， 生成 tert-butyl ((3S)-1-(4-isothiocyanato-5-isothiazolyl)-3-piperidinyl)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
• 作为产物：
  描述：

  、 (S)-3-Boc-氨基哌啶 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 生成 tert-butyl ((3S)-1-(4-nitro-5-isothiazolyl)-3-piperidinyl)carbamate
  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

文献信息

• [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。
• 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。
• Bicyclic pyridazine compounds as Pim inhibitors
  申请人：D'amico Derin C.

  公开号：US09187486B2

  公开（公告）日：2015-11-17

  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.

  本发明涉及公式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，本发明涉及包括本文所述化合物的制药组合物及其在预防和治疗Pim激酶相关的疾病和病症，尤其是癌症方面的用途。
• 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.