1,1-dimethylethyl 3-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-1-pyrrolidinecarboxylate | 937174-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1,1-dimethylethyl 3-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-1-pyrrolidinecarboxylate
• 英文别名: 1,1-dimethylethyl 3-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyI)-1-pyrrolidinecarboxylate；Tert-butyl 3-[[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methylbut-1-ynyl)imidazo[4,5-c]pyridin-7-yl]oxymethyl]pyrrolidine-1-carboxylate
• CAS: 937174-90-8
• 化学式: C₂₅H₃₃N₇O₅
• 分子量: 511.581
• InChiKey: NZESIFMKASOTDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 3-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-1-pyrrolidinecarboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以43%的产率得到4-{2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3-pyrrolidinylmethyl)oxy]-1H-imidazo[4,5-c]pyridin-4-yl}-2-methyl-3-butyn-2-oI bis-trifluoroacetic acid salt
  参考文献：
  名称：

  WO2007/58850

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(7-溴-4-氯-1-乙基-1H-咪唑并[4,5-c]吡啶-2-基)乙腈 在 四(三苯基膦)钯 sodium nitrate 、 盐酸羟胺 、 caesium carbonate 、 isopropyl magnesium chloride 、 三乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 环己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.17h， 生成 1,1-dimethylethyl 3-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  WO2008/121685

  摘要：

  公开号：

文献信息

• INHIBITORS OF AKT ACTIVITY
  申请人：Heerding Dirk A.

  公开号：US20100056523A1

  公开（公告）日：2010-03-04

  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，并用于癌症和关节炎的治疗。
• Inhibitors of Akt activity
  申请人：Heerding A. Dirk

  公开号：US20080076763A1

  公开（公告）日：2008-03-27

  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，这些化合物被用作蛋白激酶B活性的抑制剂，用于治疗癌症和关节炎。
• 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.
• US7625890B2
  申请人：——

  公开号：US7625890B2

  公开（公告）日：2009-12-01