ethyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate
• 英文别名: ethyl 1-amino-3,3-dimethyl-4H-naphthalene-2-carboxylate
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: JVFMHCNPQSGNKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate 在 sodium 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 68.5h， 生成 2-ethoxy-5,5-dimethyl-3-prop-2-enyl-6H-benzo[h]quinazolin-4-one
  参考文献：
  名称：

  Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression

  摘要：

  Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.046
• 作为产物：
  描述：

  3-甲基-2-丁烯酸乙酯 、 邻甲基苯腈 在 zinc(II) iodide 、 lithium diisopropyl amide 作用下， 生成 ethyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate
  参考文献：
  名称：

  An Efficient General Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives Based on a Tandem Conjugate Addtion-Enolate Nitrile Coupling Sequence

  摘要：

  o-(α-锂烷基)苯腈与α,β-不饱和羧酸衍生物的反应通过串联的共轭加成-烯醇腈偶联序列生成1-氨基-3,4-二氢-2-萘甲酸衍生物，而这些衍生物在与活性炭铂的脱氢反应中进一步转化为1-氨基-2-萘甲酸衍生物。

  DOI：

  10.1246/cl.1996.25

文献信息

• An Efficient General Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives Based on a Tandem Conjugate Addtion-Enolate Nitrile Coupling Sequence
  作者：Kazuhiro Kobayashi、Keiichiro Takada、Hiroto Tanaka、Tomokazu Uneda、Tomohide Kitamura、Osamu Morikawa、Hisatoshi Konishi

  DOI：10.1246/cl.1996.25

  日期：1996.1

  Reaction of o-(α-lithioalkyl)benzonitriles with α,β-unsaturated carboxylic acid derivatives produced 1-amino-3,4-dihydro-2-naphthalenecarboxylic acid derivatives through the tandem conjugate addition-enolate nitrile coupling sequence, which in turn were converted into 1-amino-2-naphthalenecarboxylic acid derivatives on dehydrogenation with palladium on activated carbon.

  o-(α-锂烷基)苯腈与α,β-不饱和羧酸衍生物的反应通过串联的共轭加成-烯醇腈偶联序列生成1-氨基-3,4-二氢-2-萘甲酸衍生物，而这些衍生物在与活性炭铂的脱氢反应中进一步转化为1-氨基-2-萘甲酸衍生物。
• Efficient Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives via a Sequential Michael Addition/Enolate−Nitrile Coupling Route and Its Application to Facile Preparation of 9-Amino Analogues of Arylnaphthofuranone Lignans
  作者：Kazuhiro Kobayashi、Tomokazu Uneda、Keiichiro Takada、Hiroto Tanaka、Tomohide Kitamura、Osamu Morikawa、Hisatoshi Konishi

  DOI：10.1021/jo961744r

  日期：1997.2.1

  2-alkylbenzonitriles with LDA in diglyme, with alpha,beta-unsaturated carboxylates and nitriles produced 1-amino-3,4-dihydro-2-naphthalenecarboxylates and carbonitriles in 54-98% yields through Michael addition of the lithio nitriles to alpha,beta-unsaturated carboxylic acid derivatives, followed by zinc iodide-promoted intramolecular enolate-nitrile coupling of the resulting enolate intermediates. The

  通过在二甘醇二甲醚中用LDA处理2-烷基苄腈与α，β-不饱和羧酸酯和腈反应原位生成的2-（α-硫代烷基）苄腈与1-氨基-3,4-二氢-2-萘甲酸乙酯和通过将硫代腈迈克尔加成到α，β-不饱和羧酸衍生物上，然后碘化锌促进分子内烯醇盐-腈偶联，生成的烯醇盐中间体以54-98％的产率形成腈。在回流的对甲基苯甲基中用活性炭上的钯脱氢，将二氢萘羧酸衍生物以43-99％的产率转化为相应的1-氨基-2-萘甲酸衍生物。随后，我们表明，通过使用类似的反应顺序，
• METHODS AND COMPOSITIONS FOR TREATING BACTERIAL INFECTION
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20150132352A1

  公开（公告）日：2015-05-14

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections (e.g., biofilms).

  本发明涉及化学化合物，它们的发现方法，以及它们的治疗和研究用途。具体而言，本发明提供了作为治疗剂抗击细菌感染（例如生物膜）的化合物。
• Methods and compositions for treating bacterial infection
  申请人：Ginsburg David

  公开号：US08501722B2

  公开（公告）日：2013-08-06

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections.

  本发明涉及化合物、其发现方法以及它们的治疗和研究用途。特别地，本发明提供了化合物作为治疗细菌感染的治疗剂。
• [EN] METHODS AND COMPOSITIONS FOR TREATING BACTERIAL INFECTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR TRAITER UNE INFECTION BACTÉRIENNE
  申请人：UNIV MICHIGAN

  公开号：WO2013166282A3

  公开（公告）日：2014-01-23