2-氨基-6,7-二甲氧基喹唑啉-4-醇 | 16175-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-氨基-6,7-二甲氧基喹唑啉-4-醇
• 中文别名: 2-氨基-6,7-二甲氧基喹唑啉-4-酮
• 英文名称: 2-amino-6,7-dimethoxyquinolizin-4(3H)-one
• 英文别名: 2-Amino-6,7-dimethoxy-3,4-dihydro-4-chinazolinon；2-amino-6,7-dimethoxy-3H-quinazolin-4-one；2-amino-6,7-dimethoxy-1H-quinazolin-4-one
• CAS: 16175-67-0
• 化学式: C₁₀H₁₁N₃O₃
• mdl: MFCD11110219
• 分子量: 221.216
• InChiKey: OEASVAKVZYHCQH-UHFFFAOYSA-N

物化性质

• 沸点：
  420.9±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氨基-6,7-二甲氧基喹唑啉-4-醇 在 三氯氧磷 作用下， 反应 8.0h， 以38%的产率得到4-氯-6,7-二甲氧基-喹唑啉-2-胺
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor

  摘要：

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

  DOI：

  10.1021/jm9503613
• 作为产物：
  描述：

  2-(ethoxycarbonylamino)-4,5-dimethoxybenzoic acid 在 三溴化磷 、 sodium carbonate 作用下， 以 乙醚 、 水 、 乙腈 为溶剂， 反应 46.25h， 生成 2-氨基-6,7-二甲氧基喹唑啉-4-醇
  参考文献：
  名称：

  2-（烷基氨基）-5,6-和-6,7-二羟基-3,4-二氢喹唑啉的合成及作为潜在多巴胺激动剂的评估。

  摘要：

  基于2-氨基二羟基-1,2,3,4-四氢萘（ADTN）的已知多巴胺能性质，制备了杂环同源物。合成了几种2-（烷基氨基）-5,6-和-6,7-二羟基-3,4-二氢喹唑啉，并测试了其在犬肾动脉中的多巴胺样血管舒张作用。6,7-二取代系列对多巴胺的拮抗作用较弱。5,6-或6,7-二羟基取代均未产生多巴胺激动剂。测得的pKa值证实了人们期望二氢喹唑啉比多巴胺更碱性，这可能是缺乏多巴胺样作用的可能原因之一。

  DOI：

  10.1021/jm00348a018

文献信息

• Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists
  作者：Serge Pieters、David McGowan、Florence Herschke、Frederik Pauwels、Bart Stoops、Stefaan Last、Werner Embrechts、Annick Scholliers、Wendy Mostmans、Kris Van Dijck、Bertrand Van Schoubroeck、Tine Thoné、Dorien De Pooter、Gregory Fanning、Mari Luz Rosauro、Mourad Daoubi Khamlichi、Ioannis Houpis、Eric Arnoult、Tim H.M. Jonckers、Pierre Raboisson

  DOI：10.1016/j.bmcl.2018.01.014

  日期：2018.2

  The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is described. The synthesis and structure-activity relationship is presented. Structural requirements and optimization of this series toward TLR 7 selectivity afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies highlighted 48 as an orally available endogenous interferon (IFN-alpha) inducer in mice. (C) 2018 Elsevier Ltd. All rights reserved.
• GROSSO, J. A.;NICHOLS, D. E.;KOHLI, J. D.;GLOCK, D., J. MED. CHEM., 1982, 25, N 6, 703-708
  作者：GROSSO, J. A.、NICHOLS, D. E.、KOHLI, J. D.、GLOCK, D.

  DOI：——

  日期：——
• Metalloprotease inhibitors containing a heterocyclic moiety
  申请人：Gege Christian

  公开号：US20080221095A1

  公开（公告）日：2008-09-11

  The present invention relates generally to pharmaceutical agents containing a heterocyclic moiety, and in particular, to heterocyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of heterocyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds with a squaramide or benzoxazinone moiety, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.
• [EN] METALLOPROTEASE INHIBITORS CONTAINING A HETEROCYCLIC MOIETY<br/>[FR] INHIBITEURS DE MÉTALLOPROTÉASES CONTENANT UNE FRACTION HÉTÉROCYCLIQUE
  申请人：ALANTOS PHARMACEUTICALS HOLDING

  公开号：WO2008109181A2

  公开（公告）日：2008-09-12

  [EN] The present invention relates generally to pharmaceutical agents containing a heterocyclic moiety, and in particular, to heterocyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of heterocyclic MMP 3, MMP 8 and/or MMP 13 inhibiting compounds with a squaramide or benzoxazinone moiety, that exhibit an increased potency and selectivity in relation to currently known MMP 13, MMP 8 and MMP 3 inhibitors.
  [FR] La présente invention porte de manière générale sur des agents pharmaceutiques contenant une fraction hétérocyclique et, en particulier, sur des composés hétérocycliques inhibiteurs de métalloprotéases. Plus particulièrement, la présente invention propose une nouvelle catégorie de composés hétérocycliques inhibiteurs de MMP 3, de MMP 8 et/ou de MMP 13 avec une fraction de squaramide ou de benzoxazinone, qui présentent une efficacité et une sélectivité accrues par rapport aux inhibiteurs de MMP 13, de MMP 8 et de MMP 3 actuellement connus.
• Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor
  作者：Alexander J. Bridges、Hairong Zhou、Donna R. Cody、Gordon W. Rewcastle、Amy McMichael、H. D. Hollis Showalter、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm9503613

  日期：1996.1.1

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.