| 1258276-82-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• CAS: 1258276-82-2
• 化学式: C₃₁H₄₂N₈O₃SSi₂
• 分子量: 662.963
• InChiKey: BGVBIILWEOULKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.75
• 重原子数：
  45.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  112.56
• 氢给体数：
  0.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 、 sodium tetrahydroborate 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成 N-[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-3-[pyridin-2-yl(pyrrolidin-1-yl)methyl]-1,2-thiazol-5-amine
  参考文献：
  名称：

  Discovery of a highly potent orally bioavailable imidazo-[1, 2- a ]pyrazine Aurora inhibitor

  摘要：

  Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.02.037
• 作为产物：
  描述：

  2-溴吡啶 、 Methyl 5-[[6-methyl-3-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]-(2-trimethylsilylethoxymethyl)amino]-1,2-thiazole-3-carboxylate 在 正丁基锂 作用下， 以74%的产率得到
  参考文献：
  名称：

  Discovery of a highly potent orally bioavailable imidazo-[1, 2- a ]pyrazine Aurora inhibitor

  摘要：

  Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.02.037

文献信息

• Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors
  作者：David B. Belanger、Michael J. Williams、Patrick J. Curran、Amit K. Mandal、Zhaoyang Meng、Matthew P. Rainka、Tao Yu、Neng-Yang Shih、M. Arshad Siddiqui、Ming Liu、Seema Tevar、Suining Lee、Lianzhu Liang、Kimberly Gray、Bohdan Yaremko、Jennifer Jones、Elizabeth B. Smith、Dan B. Prelusky、Andrea D. Basso

  DOI：10.1016/j.bmcl.2010.08.140

  日期：2010.11

  We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.