Furan-2-carboxylic acid 2,4-diamino-quinazolin-6-ylmethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: Furan-2-carboxylic acid 2,4-diamino-quinazolin-6-ylmethyl ester
• 英文别名: (2,4-Diaminoquinazolin-6-yl)methyl furan-2-carboxylate
• 化学式: C₁₄H₁₂N₄O₃
• 分子量: 284.274
• InChiKey: PBIAQMWPSLRYBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  糠酸（呋喃甲酸） 、 2,4-diamino-6-bromomethylquinazoline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以17%的产率得到Furan-2-carboxylic acid 2,4-diamino-quinazolin-6-ylmethyl ester
  参考文献：
  名称：

  Design, synthesis, and computational affinity prediction of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii

  摘要：

  A series of dihydrofolate reductase (DHFR) inhibitors, where the methylenamino-bridge of non-classical inhibitors was replaced with an ester function, have been prepared as potential soft drugs intended for inhalation against Pneumocystis carinii pneumonia (PCP). Several of the new ester-based inhibitors that should serve as good substrates for the ubiquitous esterases and possibly constitute safer alternatives to metabolically stable DHFR inhibitors administered orally, were found to be potent inhibitors of P. carinii DHFR (pcDHFR). Although the objectives of the present program is to achieve a favorable toxicity profile by applying the soft drug concept, a high preference for inhibition of the fungal DHFR versus the mammalian DHFR is still desirable to suppress host toxicity at the site of administration. Compounds with a slight preference for the fungal enzyme were identified. The selection of the target compounds for synthesis was partly guided by an automated docking and scoring procedure as well as molecular dynamics simulations. The modest selectivity of the synthesized inhibitors was reasonably well predicted, although a correct ranking of the relative affinities was not successful in all cases. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.02.004

文献信息

• Diaminoquinazoline esters for use as dihydrofolate reductase inhibitors
  申请人：——

  公开号：US20040092515A1

  公开（公告）日：2004-05-13

  Compounds of the formula I: 1 wherein R 1 , R 2 , R 1 ′ and R 2 ′ are independently hydrogen or a group releasing the free amine in vivo, R 6 is a substituted phenyl or an optionally substituted, bicyclic or tricyclic aryl ring system or an optionally substituted mono, bi- or tricyclic heteroaryl ring system having utility as DHFR inhibitors with favourable pharmacokinetic properties.

  化合物的式子为I:1，其中R1、R2、R1'和R2'独立地表示氢或在体内释放游离胺基的基团，R6表示取代的苯基或可选取代的双环或三环芳基环系统或可选取代的单环、双环或三环杂芳基环系统，具有作为DHFR抑制剂的实用性和良好的药代动力学性质。
• DIAMINOQUINAZOLINE ESTERS FOR USE AS DIHYDROFOLATE REDUCTASE INHIBITORS
  申请人：Melacure Therapeutics AB

  公开号：EP1366028A1

  公开（公告）日：2003-12-03
• [EN] DIAMINOQUINAZOLINE ESTERS FOR USE AS DIHYDROFOLATE REDUCTADE INHIBITORS<br/>[FR] ESTERS DE DIAMINOQUINAZOLINE ESTERS DESTINES A ETRE UTILISES AVEC DES INHIBITEURS DE LA DIHYDROFOLATE REDUCTASE
  申请人：MELACURE THERAPEUTICS AB

  公开号：WO2002068397A1

  公开（公告）日：2002-09-06

  Compounds of the formula (I) wherein R1, R2, R1' and R2' are independently hydrogen or a group releasing the free amine in vivo, R6 is a substituted phenyl or an optionally substituted, bicyclic or tricyclic aryl ring system or an optionally substituted mono, bi- or tricyclic heteroaryl ring system having utility as dihydrofolate reductase (DHFR) inhibitors with favourable pharmacokinetic properties.
• Design, synthesis, and computational affinity prediction of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii
  作者：Malin Graffner-Nordberg、Karin Kolmodin、Johan Åqvist、Sherry F Queener、Anders Hallberg

  DOI：10.1016/j.ejps.2004.02.004

  日期：2004.5

  A series of dihydrofolate reductase (DHFR) inhibitors, where the methylenamino-bridge of non-classical inhibitors was replaced with an ester function, have been prepared as potential soft drugs intended for inhalation against Pneumocystis carinii pneumonia (PCP). Several of the new ester-based inhibitors that should serve as good substrates for the ubiquitous esterases and possibly constitute safer alternatives to metabolically stable DHFR inhibitors administered orally, were found to be potent inhibitors of P. carinii DHFR (pcDHFR). Although the objectives of the present program is to achieve a favorable toxicity profile by applying the soft drug concept, a high preference for inhibition of the fungal DHFR versus the mammalian DHFR is still desirable to suppress host toxicity at the site of administration. Compounds with a slight preference for the fungal enzyme were identified. The selection of the target compounds for synthesis was partly guided by an automated docking and scoring procedure as well as molecular dynamics simulations. The modest selectivity of the synthesized inhibitors was reasonably well predicted, although a correct ranking of the relative affinities was not successful in all cases. (C) 2004 Elsevier B.V. All rights reserved.