4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine | 794510-70-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine
• 英文别名: 4-[5-(4-piperidinyl)-1H-pyrazol-3-yl]Pyridine；4-(5-piperidin-4-yl-1H-pyrazol-3-yl)pyridine
• CAS: 794510-70-6
• 化学式: C₁₃H₁₆N₄
• mdl: MFCD27919983
• 分子量: 228.297
• InChiKey: VXNHTGWDWVCFSI-UHFFFAOYSA-N

物化性质

• 沸点：
  463.2±45.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine 、 6-[4-(Bromomethyl)phenyl]-5-phenylnicotinonitrile 在 N,N-二异丙基乙胺 作用下， 生成 5-phenyl-6-(4-{[4-(5-pyridin-4-yl-1H-pyrazol-3-yl)piperidin-1-yl]methyl}phenyl)nicotinonitrile
  参考文献：
  名称：

  Optimization of 2,3,5-trisubstituted pyridine derivatives as potent allosteric Akt1 and Akt2 inhibitors

  摘要：

  This letter shows inhibitor SAR on a pyridine series of allosteric Akt inhibitors to optimize enzymatic and cellular potency. We have optimized 2,3,5-trisubstituted pyridines to give potent Akt1 and Akt2 inhibitors in both enzyme and cell based assays. In addition, we will also highlight the pharmacokinetic pro. le of an optimized inhibitor that has low clearance and long half-life in dogs. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.040
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 一水合肼 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine
  参考文献：
  名称：

  发现 D25，一种有效的选择性 MNK 抑制剂，用于治疗脓毒症相关急性脾损伤

  摘要：

  丝裂原活化蛋白激酶相互作用蛋白激酶 （MNK） 和磷酸化真核起始因子 4E （p-eIF4E） 在调节与癌症发展、代谢和炎症相关的 mRNA 翻译和蛋白质合成中起关键作用。本研究对 4-（3-（哌啶-4-基）-1H-吡唑-5-基）吡啶结构进行了修饰，从而发现了 4-（3-（哌啶-4-基）-1H-吡唑-5-基）-1H-吡咯并[2,3-b]吡啶 （D25） 作为一种有效的选择性 MNK 抑制剂。D25 显示出抑制活性，MNK1 的 IC 50 值为 120.6 nM，MNK2 的 IC50 值为 134.7 nM，显示出卓越的选择性。D25 抑制 RAW264.7 细胞中促炎细胞因子的表达，如诱导型 NO 合酶、环氧合酶-2 和白细胞介素-6 （IL-6）。在脂多糖诱导的脓毒症小鼠模型中，D25 显著降低脾组织中的 p-eIF4E，降低肿瘤坏死因子 α、白细胞介素-1β 和 IL-6 的表达，

  DOI：

  10.1021/acs.jmedchem.3c02441

文献信息

• Inhibitors of akt activity
  申请人：Bilodeau T Mark

  公开号：US20070043001A1

  公开（公告）日：2007-02-22

  The present invention is directed to compounds which contain a substituted pyridine moeity which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

  本发明涉及化合物，其中包含取代的吡啶基团，可抑制Akt蛋白激酶的活性。本发明还涉及含有本发明化合物的化疗组合物和治疗癌症的方法，包括给予本发明化合物的治疗方法。
• Development of Pyridopyrimidines as Potent Akt1/2 Inhibitors
  作者：Zhicai Wu、John C. Hartnett、Lou Anne Neilson、Ronald G. Robinson、Sheng Fu、Stanley F. Barnett、Deborah Defeo-Jones、Raymond E. Jones、Astrid M. Kral、Hans E. Huber、George D. Hartman、Mark T. Bilodeau

  DOI：10.1016/j.bmcl.2008.01.054

  日期：2008.2

  This communication reports a new synthetic route of pyridopyrimidines to facilitate their structural optimization in a library fashion and describes the development of pyridopyrimidines that have excellent enzymatic and cell potency against Akt1 and Akt2. This series also shows a high level of selectivity over other closely related kinases and significantly improved caspase-3 activity with the more optimized compounds. (c) 2008 Published by Elsevier Ltd.
• Allosteric inhibitors of Akt1 and Akt2: A naphthyridinone with efficacy in an A2780 tumor xenograft model
  作者：Mark T. Bilodeau、Adrienne E. Balitza、Jacob M. Hoffman、Peter J. Manley、Stanley F. Barnett、Deborah Defeo-Jones、Kathleen Haskell、Raymond E. Jones、Karen Leander、Ronald G. Robinson、Anthony M. Smith、Hans E. Huber、George D. Hartman

  DOI：10.1016/j.bmcl.2008.04.074

  日期：2008.6

  A series of naphthyridine and naphthyridinone allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been optimized to have potent dual activity against the activated kinase as well as the activation of Akt in cells. One molecule in particular, compound 17, has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model. (C) 2008 Elsevier Ltd. All rights reserved.
• Rapid assembly of diverse and potent allosteric Akt inhibitors
  作者：Zhicai Wu、Ronald G. Robinson、Sheng Fu、Stanley F. Barnett、Deborah Defeo-Jones、Raymond E. Jones、Astrid M. Kral、Hans E. Huber、Nancy E. Kohl、George D. Hartman、Mark T. Bilodeau

  DOI：10.1016/j.bmcl.2007.10.023

  日期：2008.3

  This paper describes the rapid assembly of four different classes of potent Akt inhibitors from a common intermediate. Among them, a pyridopyrimidine series displayed the best intrinsic and cell potency against Akt1 and Akt2. This series also showed a promising pharmacokinetic pro. le and excellent selectivity over other closely related kinases. (C) 2008 Published by Elsevier Ltd.
• INHIBITORS OF AKT ACTIVITY
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1622616B1

  公开（公告）日：2011-06-15