N-(4-{[7-(2-hydroxyethoxy)-6-methoxyquinazolin-4-yl]amino}phenyl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-{[7-(2-hydroxyethoxy)-6-methoxyquinazolin-4-yl]amino}phenyl)benzamide
• 英文别名: N-[4-[[7-(2-hydroxyethoxy)-6-methoxyquinazolin-4-yl]amino]phenyl]benzamide
• 化学式: C₂₄H₂₂N₄O₄
• 分子量: 430.463
• InChiKey: YBJZSILFXVVNBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氨基苯甲酰苯胺 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 N-(4-{[7-(2-hydroxyethoxy)-6-methoxyquinazolin-4-yl]amino}phenyl)benzamide
  参考文献：
  名称：

  Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping

  摘要：

  An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J. 2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.08.017

文献信息

• QUINAZOLINE DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
  申请人：AstraZeneca AB

  公开号：EP1218354A1

  公开（公告）日：2002-07-03
• US7709479B1
  申请人：——

  公开号：US7709479B1

  公开（公告）日：2010-05-04
• [EN] QUINAZOLINE DERIVATIVES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] DERIVES DE QUINAZOLINE ET LEUR UTILISATION COMME PRODUITS PHARMACEUTIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2001021596A1

  公开（公告）日：2001-03-29

  The use of a compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O) or S(O)2, NH or NR12 where R12 is hydrogen or C¿1-6? alkyl; R?5¿ is selected from a group NHC(O)OR9, NHC(O)R9, NHS(O)¿2?R?9, C(O)R9¿, C(O)OR?9, S(O)R9¿, S(O)OR9, S(O)¿2OR?9, C(O)NR10 R11, S(O)NR10R11 S(O)ONR10R11, where R?9, R10 or R11¿ are various specified organic groups; R6 is hydrogen, optionally substituted hydrocarbyl or optionally substituted heterocyclyl; R?7 and R8¿ are various specified organic groups, and R?1, R2, R3, R4¿ are independently selected from halogeno, cyano, nitro, C¿1-3?alkylsulphanyl, -N(OH)R?13¿-(wherein R7 is hydrogen, or C¿1-3?alkyl), or R?15X1¿-(wherein X1 represents a direct bond, -O-, -CH¿2?-, -OCO-, carbonyl, -S-, -SO-, -SO2-, -NR?16¿CO-, -CONR16-, -SO¿2?NR?16-, -NR17SO¿2- or -NR18-(wherein R?16, R17 and R18¿ each independently represents hydrogen, C¿1-3?alkyl or C1-3alkoxy C2-3alkyl), and R?9¿ is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; in the preparation of a medicament for use in the inhibition of aurora 2 kinase.
• Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping
  作者：Peter Doig、P. Ann Boriack-Sjodin、Jacques Dumas、Jun Hu、Kenji Itoh、Kenneth Johnson、Steven Kazmirski、Tomohiko Kinoshita、Satoru Kuroda、Tomo-o Sato、Kaori Sugimoto、Katsumi Tohyama、Hiroshi Aoi、Kazusa Wakamatsu、Hongming Wang

  DOI：10.1016/j.bmc.2014.08.017

  日期：2014.11

  An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J. 2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class. (C) 2014 Elsevier Ltd. All rights reserved.