2-[2-[(1-Aminoisoquinolin-6-yl)carbamoyl]-6-ethenylpyridin-3-yl]-5-(2,2-dimethylpropylcarbamoyl)benzoic acid | 431052-60-7

• 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: 2-[2-[(1-Aminoisoquinolin-6-yl)carbamoyl]-6-ethenylpyridin-3-yl]-5-(2,2-dimethylpropylcarbamoyl)benzoic acid
• CAS: 431052-60-7
• 化学式: C₃₀H₂₉N₅O₄
• 分子量: 523.591
• InChiKey: RDEWVVNVZDTDJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl 2-[2-[[1-[(2,4-dimethoxyphenyl)methylamino]isoquinolin-6-yl]carbamoyl]-6-oxo-1H-pyridin-3-yl]-5-(2,2-dimethylpropylcarbamoyl)benzoate 在 bis-triphenylphosphine-palladium(II) chloride 、 苯甲醚 、 三乙胺 、 三氟乙酸 、 copper(II) oxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[2-[(1-Aminoisoquinolin-6-yl)carbamoyl]-6-ethenylpyridin-3-yl]-5-(2,2-dimethylpropylcarbamoyl)benzoic acid
  参考文献：
  名称：

  Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold

  摘要：

  In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIla inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIla is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor Vlla. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.06.028

文献信息

• Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold
  作者：Scott A. Bolton、James C. Sutton、Rushith Anumula、Gregory S. Bisacchi、Bruce Jacobson、William A. Slusarchyk、Uwe D. Treuner、Shung C. Wu、Guohua Zhao、Zulan Pi、Steven Sheriff、Rebecca A. Smirk、Sharon Bisaha、Daniel L. Cheney、Anzhi Wei、William A. Schumacher、Karen S. Hartl、Eddie Liu、Robert Zahler、Steven M. Seiler

  DOI：10.1016/j.bmcl.2013.06.028

  日期：2013.9

  In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIla inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIla is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor Vlla. (C) 2013 Published by Elsevier Ltd.