3-(3-(4-(tert-butyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-pyridin-2-amine | 1313878-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-(4-(tert-butyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-pyridin-2-amine
• 英文别名: 3-(1-(4-(tert-butyl)phenyl)-1H-benzo[d]imidazol-2-yl)pyridin-2-amine；3-(3-(4-(tert-butyl)phenyl)-3H-imidazo[4,5-b]pyridine-2-yl)pyridine-2-amine；3-[3-(4-Tert-butylphenyl)imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine
• CAS: 1313878-10-2
• 化学式: C₂₁H₂₁N₅
• 分子量: 343.431
• InChiKey: ZRZWDPLGTAJRFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯-3-硝基吡啶 在 sodium dithionite 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成 3-(3-(4-(tert-butyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-pyridin-2-amine
  参考文献：
  名称：

  Discovery and Optimization of a Series of 3-(3-Phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: Orally Bioavailable, Selective, and Potent ATP-Independent Akt Inhibitors

  摘要：

  This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 A, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected. These Akt inhibitors potently inhibit intracellular Akt activation and its downstream target (PRAS40) in vitro. In vivo pharmacodynamic and pharmacokinetic studies with two examples, 12e and 12j, showed the series to be similarly effective at inhibiting the activation of Akt and and additional downstream effector (p70S6) following oral dosing in mice.

  DOI：

  10.1021/jm300276x

文献信息

• Substituted Imidazopyridinyl-Aminopyridine Compounds
  申请人：Ashwell Mark A.

  公开号：US20110172203A1

  公开（公告）日：2011-07-14

  The present invention relates to substituted imidazopyridinyl-aminopyridine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted imidazopyridinyl-aminopyridine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及取代咪唑吡啶基-氨基吡啶化合物及合成这些化合物的方法。本发明还涉及含有取代咪唑吡啶基-氨基吡啶化合物的药物组合物，以及通过向需要的受试者施用这些化合物和药物组合物来治疗细胞增殖性疾病，如癌症的方法。
• Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor
  作者：Jean-Marc Lapierre、Sudharshan Eathiraj、David Vensel、Yanbin Liu、Cathy O. Bull、Susan Cornell-Kennon、Shin Iimura、Eugene W. Kelleher、Darin E. Kizer、Steffi Koerner、Sapna Makhija、Akihisa Matsuda、Magdi Moussa、Nivedita Namdev、Ronald E. Savage、Jeff Szwaya、Erika Volckova、Neil Westlund、Hui Wu、Brian Schwartz

  DOI：10.1021/acs.jmedchem.6b00619

  日期：2016.7.14

  potent, selective allosteric inhibitors of AKT kinases, leading to the discovery of ARQ 092 (21a). The cocrystal structure of compound 21a bound to full-length AKT1 confirmed the allosteric mode of inhibition of this chemical class and the role of the cyclobutylamine moiety. Compound 21a demonstrated high enzymatic potency against AKT1, AKT2, and AKT3, as well as potent cellular inhibition of AKT activation

  本文的工作描述了3-（3-苯基-3 H-咪唑并[4,5 - b ]吡啶-2-基）吡啶-2-胺化学系列的优化，作为AKT激酶的有效，选择性变构抑制剂，导致发现了ARQ 092（21a）。与全长AKT1结合的化合物21a的共晶体结构证实了该化学类别的变构抑制模式以及环丁胺部分的作用。化合物21a对AKT1，AKT2和AKT3具有很高的酶促效力，并且对AKT活化和下游靶标PRAS40的磷酸化具有强大的细胞抑制作用。化合物21a 它还在人子宫内膜腺癌异种移植小鼠模型中用作AKT1-E17K突变蛋白的有效抑制剂，并抑制肿瘤生长。
• SUBSTITUTED IMIDAZOPYRIDINYL-AMINOPYRIDINE COMPOUNDS
  申请人：ArQule, Inc.

  公开号：EP2519522A2

  公开（公告）日：2012-11-07
• US8501770B2
  申请人：——

  公开号：US8501770B2

  公开（公告）日：2013-08-06
• [EN] SUBSTITUTED IMIDAZOPYRIDINYL-AMINOPYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS IMIDAZOPYRIDINYL-AMINOPYRIDINE SUBSTITUÉS
  申请人：ARQULE INC

  公开号：WO2011082270A2

  公开（公告）日：2011-07-07

  The present invention relates to substituted imidazopyridinyl-aminopyridine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted imidazopyridinyl- aminopyridine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.