N,N’-di(tert-butoxycarbonyl)-N’’-(3-cyanophenyl)guanidine | 1257531-12-6

• 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,N’-di(tert-butoxycarbonyl)-N’’-(3-cyanophenyl)guanidine
• 英文别名: 1-(3-cyanophenyl)-2,3-di-Boc-guanidine；tert-butyl N-[N'-(3-cyanophenyl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1257531-12-6
• 化学式: C₁₈H₂₄N₄O₄
• 分子量: 360.413
• InChiKey: VZPVMAYAZBBWQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N’-di(tert-butoxycarbonyl)-N’’-(3-cyanophenyl)guanidine 在 palladium 10% on activated carbon 、 氨 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、310.27 kPa 条件下， 反应 9.0h， 以52.7%的产率得到3-[[bis[[(1,1-dimethylethoxy)carbonyl]amino]methylene]amino]benzylamine
  参考文献：
  名称：

  Specificity of a Prodrug-Activating Enzyme hVACVase: The Leaving Group Effect

  摘要：

  Human valacyclovirase (hVACVase) is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of new prodrugs targeting hVACVase activation. In this study, a series of valine esters, phenylalanine esters, and a valine amide were characterized for the effect of the leaving group on the efficiency of hVACVase-mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibited a relatively high specificity constant (k(cat)/K-m), ranging from 850 to 9490 mM(-1).s(-1). The valine amide Val-3-APG exhibited significantly higher K-m and lower k(cat) values compared to the corresponding ester Val-3-HPG, indicating poor specificity for hVACVase. In conclusion, the substrate leaving group has been shown to affect both binding and specific activity of hVACVase-catalyzed activation. It is proposed that hVACVase is an ideal target for a-amino acid ester prodrugs with relatively labile leaving groups while it is relatively inactivate toward amide prodrugs.

  DOI：

  10.1021/mp100300k
• 作为产物：
  描述：

  间氨基苯甲腈 、 N,N'-bis-Boc-S-methyl-isothiourea 在 三乙胺 、 mercury dichloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以91%的产率得到N,N’-di(tert-butoxycarbonyl)-N’’-(3-cyanophenyl)guanidine
  参考文献：
  名称：

  Specificity of a Prodrug-Activating Enzyme hVACVase: The Leaving Group Effect

  摘要：

  Human valacyclovirase (hVACVase) is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of new prodrugs targeting hVACVase activation. In this study, a series of valine esters, phenylalanine esters, and a valine amide were characterized for the effect of the leaving group on the efficiency of hVACVase-mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibited a relatively high specificity constant (k(cat)/K-m), ranging from 850 to 9490 mM(-1).s(-1). The valine amide Val-3-APG exhibited significantly higher K-m and lower k(cat) values compared to the corresponding ester Val-3-HPG, indicating poor specificity for hVACVase. In conclusion, the substrate leaving group has been shown to affect both binding and specific activity of hVACVase-catalyzed activation. It is proposed that hVACVase is an ideal target for a-amino acid ester prodrugs with relatively labile leaving groups while it is relatively inactivate toward amide prodrugs.

  DOI：

  10.1021/mp100300k

文献信息

• [EN] ISOQUINOLINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS D'ISOQUINOLINONE UTILES DANS LE TRAITEMENT DU CANCER
  申请人：PF MEDICAMENT

  公开号：WO2016034642A1

  公开（公告）日：2016-03-10

  The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as a drug, notably in the treatment of cancer, as well as pharmaceutical compositions containing such a compound and processes to prepare such a compound.

  本发明涉及以下式（I）的化合物或其药学上可接受的盐和/或溶剂化合物，特别用作药物，特别用于治疗癌症，以及含有这种化合物的药物组合物和制备这种化合物的方法。
• Discovery, synthesis, and structure–activity relationships of 2-aminoquinazoline derivatives as a novel class of metabotropic glutamate receptor 5 negative allosteric modulators
  作者：Holger Kubas、Udo Meyer、Bjoern Krueger、Mirko Hechenberger、Maksims Vanejevs、Ronalds Zemribo、Valerjans Kauss、Raisa Ambartsumova、Ilya Pyatkin、Alexey I. Polosukhin、Ulrich Abel

  DOI：10.1016/j.bmcl.2013.06.049

  日期：2013.8

  A virtual screening approach using various in silico methodologies led to the discovery of 2-(m-tolylamino)-7,8-dihydroquinazolin-5(6H)-one (1) as a moderately active negative allosteric modulator (NAM) of the metabotropic glutamate receptor subtype 5 (mGluR5) showing high selectivity against the subtype mGluR1. Modifications of the parent compound by rational design yielded a series of highly potent derivatives which will serve as valuable starting points for further hit-to-lead optimization efforts toward a suitable drug candidate for the treatment of L-DOPA induced dyskinesia. (c) 2013 Elsevier Ltd. All rights reserved.
• ISOQUINOLINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER
  申请人：Pierre Fabre Médicament

  公开号：EP3189051A1

  公开（公告）日：2017-07-12
• US9944641B2
  申请人：——

  公开号：US9944641B2

  公开（公告）日：2018-04-17