[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-isoquinolin-6-ylamino]-(3-ethoxy-4-isopropoxy-phenyl)-acetic acid | 745019-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: [1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-isoquinolin-6-ylamino]-(3-ethoxy-4-isopropoxy-phenyl)-acetic acid
• 英文别名: 2-[[1-(1,3-Dioxoisoindol-2-yl)isoquinolin-6-yl]amino]-2-(3-ethoxy-4-propan-2-yloxyphenyl)acetic acid
• CAS: 745019-98-1
• 化学式: C₃₀H₂₇N₃O₆
• 分子量: 525.561
• InChiKey: YCTUYNOVUXLPIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-isoquinolin-6-ylamino]-(3-ethoxy-4-isopropoxy-phenyl)-acetic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[(1-aminoisoquinolin-6-yl)amino]-2-(3-ethoxy-4-propan-2-yloxyphenyl)-N-(3-hydroxyphenyl)sulfonylacetamide
  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
• 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 、 caesium carbonate 、 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 、 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 [1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-isoquinolin-6-ylamino]-(3-ethoxy-4-isopropoxy-phenyl)-acetic acid
  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

• Phenylglycine derivatives useful as serine protease inhibitors
  申请人：——

  公开号：US20040204412A1

  公开（公告）日：2004-10-14

  Compounds having the formula (I), 1 or a stereoisomer or pharmaceutically-acceptable salt, or hydrate thereof, are useful as factor VIIa inhibitors, wherein X is —NR 6 S(O) p R 16 ; W is hydrogen or —(CR 7 R 8 ) q W 1 ; W 1 is hydrogen or a bond with R 6 ; 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 R 1 , R 2 , R 3 , R 6 , R 7 , and R 16 are as defined in the specification.

  具有公式（I）的化合物，或其立体异构体或药学上可接受的盐或水合物，可用作因子VIIa抑制剂，其中X为—NR6S(O)pR16；W为氢或—(CR7R8)qW1；W1为氢或与R6相连的键；Z为5-成员杂芳基团，五至六成员杂环或环烷基团，9-至10-成员双环芳基或杂芳基，或六成员芳基或杂芳基，而R1、R2、R3、R6、R7和R16如说明书所定义。
• US7122559B2
  申请人：——

  公开号：US7122559B2

  公开（公告）日：2006-10-17
• [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.