tert-butyl 4-((2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yloxy)methyl)piperidine-1-carboxylate | 842149-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-((2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yloxy)methyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[[2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethylimidazo[4,5-c]pyridin-7-yl]oxymethyl]piperidine-1-carboxylate
• CAS: 842149-07-9
• 化学式: C₂₁H₂₈ClN₇O₄
• 分子量: 477.951
• InChiKey: HWDJCHJUCCGCQN-UHFFFAOYSA-N

物化性质

• 沸点：
  668.9±65.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yloxy)methyl)piperidine-1-carboxylate 、 盐酸 在 甲醇 作用下， 以 甲醇 、 1,4-二氧六环 为溶剂， 反应 3.0h， 以to yield the desired product as a white powder (0.0185 g, 46%)的产率得到4-(4-chloro-1-ethyl-7-(piperidin-4-ylmethoxy)-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine formate salt
  参考文献：
  名称：

  METHODS FOR THE IDENTIFICATION OF PARP INTERACTING MOLECULES AND FOR PURIFICATION OF PARP PROTEINS

  摘要：

  本发明涉及用于鉴定PARP相互作用化合物或用于纯化或鉴定PARP蛋白质的固定化化合物和方法。

  公开号：

  US20110070595A1
• 作为产物：
  描述：

  2-(4-氨基-1,2,5-噁二唑-3-基)-4-氯-1-乙基-1H-咪唑并[4,5-c]吡啶-7-醇 、 1-Boc-4-溴甲基哌啶 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 tert-butyl 4-((2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yloxy)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase

  摘要：

  Overexpression of AKT has an antiapoptotic effect in many cell types, and expression of dominant negative AKT blocks the ability of a variety of growth factors to promote survival. Therefore, inhibitors of AKT kinase activity might be useful as monotherapy for the treatment of tumors with activated AKT. Herein, we describe our lead optimization studies culminating in the discovery of compound 3g (GSK690693). Compound 3g is a novel ATP competitive, pan-AKT kinase inhibitor with IC 50 values of 2, 13, and 9 nM against AKT1, 2, and 3, respectively. An X-ray cocrystal structure was solved with 3g and the kinase domain of AKT2, confirming that 3g bound in the ATP binding pocket. Compound 3g potently inhibits intracellular AKT activity as measured by the inhibition of the phosphorylation levels of GSK3beta. Intraperitoneal administration of 3g in immunocompromised mice results in the inhibition of GSK3beta phosphorylation and tumor growth in human breast carcinoma (BT474) xenografts.

  DOI：

  10.1021/jm8004527

文献信息

• [EN] INHIBITORS OF Akt ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITE DE AKT
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005011700A1

  公开（公告）日：2005-02-10

  Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yI compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  发明了新型的1H-咪唑[4,5-c]吡啶-2-基化合物，这些化合物用作蛋白激酶B活性的抑制剂，并用于治疗癌症和关节炎。
• Inhibitors of Akt Activity
  申请人：Heerding Dirk A.

  公开号：US20080255143A1

  公开（公告）日：2008-10-16

  Invented are novel 1H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  发明了新型的1H-咪唑[4,5-c]吡啶-2-基化合物，这些化合物可用作蛋白激酶B活性抑制剂，并用于癌症和关节炎的治疗。
• EP1653961A4
  申请人：——

  公开号：EP1653961A4

  公开（公告）日：2009-04-01
• INHIBITORS OF AKT ACTIVITY
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1653961A1

  公开（公告）日：2006-05-10
• Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3<i>S</i>)-3-piperidinylmethyl]oxy}-1<i>H</i>-imidazo[4,5-<i>c</i>]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase
  作者：Dirk A. Heerding、Nelson Rhodes、Jack D. Leber、Tammy J. Clark、Richard M. Keenan、Louis V. Lafrance、Mei Li、Igor G. Safonov、Dennis T. Takata、Joseph W. Venslavsky、Dennis S. Yamashita、Anthony E. Choudhry、Robert A. Copeland、Zhihong Lai、Michael D. Schaber、Peter J. Tummino、Susan L. Strum、Edgar R. Wood、Derek R. Duckett、Derek Eberwein、Victoria B. Knick、Timothy J. Lansing、Randy T. McConnell、ShuYun Zhang、Elisabeth A. Minthorn、Nestor O. Concha、Gregory L. Warren、Rakesh Kumar

  DOI：10.1021/jm8004527

  日期：2008.9.25

  Overexpression of AKT has an antiapoptotic effect in many cell types, and expression of dominant negative AKT blocks the ability of a variety of growth factors to promote survival. Therefore, inhibitors of AKT kinase activity might be useful as monotherapy for the treatment of tumors with activated AKT. Herein, we describe our lead optimization studies culminating in the discovery of compound 3g (GSK690693). Compound 3g is a novel ATP competitive, pan-AKT kinase inhibitor with IC 50 values of 2, 13, and 9 nM against AKT1, 2, and 3, respectively. An X-ray cocrystal structure was solved with 3g and the kinase domain of AKT2, confirming that 3g bound in the ATP binding pocket. Compound 3g potently inhibits intracellular AKT activity as measured by the inhibition of the phosphorylation levels of GSK3beta. Intraperitoneal administration of 3g in immunocompromised mice results in the inhibition of GSK3beta phosphorylation and tumor growth in human breast carcinoma (BT474) xenografts.