tert-butyl (5-nitro-4-(piperidin-1-yl)pyrimidin-2-yl)carbamate | 1469924-85-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: tert-butyl (5-nitro-4-(piperidin-1-yl)pyrimidin-2-yl)carbamate
• CAS: 1469924-85-3
• 化学式: C₁₄H₂₁N₅O₄
• 分子量: 323.352
• InChiKey: HMNQXLUPJLSAEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.72
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  110.49
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-nitro-4-(piperidin-1-yl)pyrimidin-2-yl)carbamate 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 63.0h， 生成 tert-butyl (5-(2-acetamidothiazole-4-carboxamido)-4-(piperidin-1-yl)pyrimidin-2-yl)carbamate
  参考文献：
  名称：

  Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors

  摘要：

  Proviral insertion of Moloney virus (PIM) 1, 2, and 3 kinases are serine/threonine kinases that normally function in survival and proliferation of hematopoietic cells. As high expression of PIM1, 2, and 3 is frequently observed in many human malignancies, including multiple myeloma, non Hodgkins lymphoma, and myeloid leukemias, there is interest in determining whether selective PIM1 inhibition can improve outcomes of these human cancers. Herein, we describe our efforts toward this goal. The structure guided optimization of a singleton high throughput screening hit in which the potency against all three PIM isoforms was increased >10,000 fold to yield compounds with pan PIM K(i)s < 10 pM, nanomolar cellular potency, and in vivo activity in an acute myeloid leukemia Pun dependent tumor model is described.

  DOI：

  10.1021/ml400307j
• 作为产物：
  描述：

  2-氯-5-硝基-4-(哌啶-1-基)嘧啶 在 氨 作用下， 以 甲醇 、 叔丁醇 为溶剂， 反应 144.0h， 生成 tert-butyl (5-nitro-4-(piperidin-1-yl)pyrimidin-2-yl)carbamate
  参考文献：
  名称：

  Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors

  摘要：

  Proviral insertion of Moloney virus (PIM) 1, 2, and 3 kinases are serine/threonine kinases that normally function in survival and proliferation of hematopoietic cells. As high expression of PIM1, 2, and 3 is frequently observed in many human malignancies, including multiple myeloma, non Hodgkins lymphoma, and myeloid leukemias, there is interest in determining whether selective PIM1 inhibition can improve outcomes of these human cancers. Herein, we describe our efforts toward this goal. The structure guided optimization of a singleton high throughput screening hit in which the potency against all three PIM isoforms was increased >10,000 fold to yield compounds with pan PIM K(i)s < 10 pM, nanomolar cellular potency, and in vivo activity in an acute myeloid leukemia Pun dependent tumor model is described.

  DOI：

  10.1021/ml400307j