3-[[2-[(1-Aminoisoquinolin-6-yl)amino]-2-(3-ethoxy-4-propan-2-yloxyphenyl)acetyl]sulfamoyl]benzamide | 745019-76-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-[[2-[(1-Aminoisoquinolin-6-yl)amino]-2-(3-ethoxy-4-propan-2-yloxyphenyl)acetyl]sulfamoyl]benzamide
• CAS: 745019-76-5
• 化学式: C₂₉H₃₁N₅O₆S
• 分子量: 577.661
• InChiKey: XMYBUOHBAIWKLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  184
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-乙氧基-4-异丙氧基苯甲醛 在 盐酸 、 palladium 10% on activated carbon 、 水 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 caesium carbonate 、 一水合肼 、 sodium hydrogensulfite 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、413.7 kPa 条件下， 反应 66.0h， 生成 3-[[2-[(1-Aminoisoquinolin-6-yl)amino]-2-(3-ethoxy-4-propan-2-yloxyphenyl)acetyl]sulfamoyl]benzamide
  参考文献：
  名称：

  Nonbenzamidine acylsulfonamide tissue factor–factor VIIa inhibitors

  摘要：

  Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor Vila inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.027

文献信息

• [EN] PHENYLGLYCINE DERIVATIVES USEFUL AS SERINE PROTEASE INHIBITORS<br/>[FR] DERIVES DE PHENYLGLYCINE UTILES EN TANT QU'INHIBITEURS DE SERINE PROTEASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004072101A2

  公开（公告）日：2004-08-26

  Compounds having the formula (I), or a stereoisomer or pharmaceutically-acceptable salt, or hydrate thereof, are useful as factor VIIa inhibitors, wherein X is NR6S(O)pR16; W is hydrogen or (CR7R8)q­- W1; W1 is hydrogen or a bond with R6; Z is a 5-membered heteroaryl group, a five to six membered heterocyclo or cycloalkyl group, a 9 to 10 membered bicyclic aryl or heteroaryl, or a six membered aryl or heteroaryl, and R1, R2, R3 , R6, R7, and R16 are as defined in the specification.
• Nonbenzamidine acylsulfonamide tissue factor–factor VIIa inhibitors
  作者：Peter W. Glunz、Xiaojun Zhang、Yan Zou、Indawati Delucca、Alexandra H. Nirschl、Xuhong Cheng、Carolyn A. Weigelt、Daniel L. Cheney、Anzhi Wei、Rushith Anumula、Joseph M. Luettgen、Alan R. Rendina、Mark Harpel、Gang Luo、Robert Knabb、Pancras C. Wong、Ruth R. Wexler、E. Scott Priestley

  DOI：10.1016/j.bmcl.2013.06.027

  日期：2013.9

  Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor Vila inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype. (C) 2013 Elsevier Ltd. All rights reserved.