[4-(tert-butyldimethylsilanyloxymethyl)pyridin-2-yl](5-phenylthiazol-2-yl)amine | 329794-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [4-(tert-butyldimethylsilanyloxymethyl)pyridin-2-yl](5-phenylthiazol-2-yl)amine
• 英文别名: N-(4-(((tert-butyldimethylsilyl)oxy)methyl)pyridin-2-yl)-5-phenylthiazol-2-amine；N-[4-[[tert-butyl(dimethyl)silyl]oxymethyl]pyridin-2-yl]-5-phenyl-1,3-thiazol-2-amine
• CAS: 329794-10-7
• 化学式: C₂₁H₂₇N₃OSSi
• 分子量: 397.616
• InChiKey: VEQQDEYHWDOIEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.47
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(tert-butyldimethylsilanyloxymethyl)pyridin-2-yl](5-phenylthiazol-2-yl)amine 在 氟化氢吡啶 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 [4-(4-methanesulfonyl-piperazin-1-ylmethyl)-pyridin-2-yl]-(5-phenyl-thiazol-2-yl)-amine
  参考文献：
  名称：

  Potent N-(1,3-Thiazol-2-yl)pyridin-2-amine Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors with Excellent Pharmacokinetics and Low Affinity for the hERG Ion Channel

  摘要：

  A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.

  DOI：

  10.1021/jm049697f
• 作为产物：
  描述：

  (2-氯吡啶-4-基)甲醇 在 咪唑 、 tris(dibenzylideneacetone)dipalladium (0) 、 羟胺 、 sodium hydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 49.0h， 生成 [4-(tert-butyldimethylsilanyloxymethyl)pyridin-2-yl](5-phenylthiazol-2-yl)amine
  参考文献：
  名称：

  Potent N-(1,3-Thiazol-2-yl)pyridin-2-amine Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors with Excellent Pharmacokinetics and Low Affinity for the hERG Ion Channel

  摘要：

  A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.

  DOI：

  10.1021/jm049697f

文献信息

• Potent <i>N</i>-(1,3-Thiazol-2-yl)pyridin-2-amine Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors with Excellent Pharmacokinetics and Low Affinity for the hERG Ion Channel
  作者：Mark T. Bilodeau、Adrienne E. Balitza、Timothy J. Koester、Peter J. Manley、Leonard D. Rodman、Carolyn Buser-Doepner、Kathleen E. Coll、Christine Fernandes、Jackson B. Gibbs、David C. Heimbrook、William R. Huckle、Nancy Kohl、Joseph J. Lynch、Xianzhi Mao、Rosemary C. McFall、Debra McLoughlin、Cynthia M. Miller-Stein、Keith W. Rickert、Laura Sepp-Lorenzino、Jennifer M. Shipman、Raju Subramanian、Kenneth A. Thomas、Bradley K. Wong、Sean Yu、George D. Hartman

  DOI：10.1021/jm049697f

  日期：2004.12.1

  A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.