104479-00-7Relevant articles and documents
Synthesis and structure-activity relationships of (aryloxy)quinazoline ureas as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors
Garofalo, Antonio,Farce, Amaury,Ravez, Séverine,Lemoine, Amélie,Six, Perrine,Chavatte, Philippe,Goossens, Laurence,Depreux, Patrick
scheme or table, p. 1189 - 1204 (2012/03/27)
In our continuing search for medicinal agents to treat proliferative diseases, quinazoline derivatives were synthesized and evaluated pharmacologically as epithelial growth factor receptor and vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitors. A quantitative structure-activity relationship analysis was conducted to rationalize the structure-activity relationship and to predict how similar the inhibitor-binding profiles of two protein kinases are likely to be on the basis of the docking of lead coumpounds into the ATP-binding site. This model was used to direct the synthesis of new compounds. A series of N-(aromatic)-N′-{4-[(6,7- dimethoxyquinazolin-4-yl)oxy]phenyl}urea were identified as potent and selective inhibitors of the tyrosine kinase activity of VEGFR-2 (fetal liver kinase 1, kinase insert domain-containing receptor). An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. Substitution of diarylurea, competitive with ATP, afforded several analogues with low nanomolar inhibition of enzymatic activity of VEGFR-2. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of the series.
Novel and efficient one-pot synthesis of (aminophenyl)carbamic acid esters
Garofalo, Antonio,Goossens, Laurence,Six, Perrine,Lebegue, Nicolas,Depreux, Patrick
experimental part, p. 2007 - 2016 (2011/06/24)
A novel and efficient protocol is developed for the synthesis of various (aminophenyl) carbamic acid esters from the reduction and condensation of nitrophenyl isocyanate derivatives. The reaction takes place in various hydroxy derivatives such as alcohols or phenols under a hydrogen atmosphere using Raney nickel as catalyst. Products are obtained by a convenient one-pot synthesis with excellent yields and short reaction times.
Quinone Imine Route to Benzimidazol-2-ylcarbamates. Part 1. Synthesis of Open-chain and Cyclic 5-Acylamino Derivatives.
Rajappa, Srinivasachari,Sreenivasan, Ramaswami,Khalwadekar, Asha
, p. 1657 - 1675 (2007/10/02)
The synthesis of the N',N''-bismethoxycarbonyl-N-(4-acylaminophenyl)guanidines (4) and (7) is described.Oxidation of these with LTA has led to the benzimidazol-2-ylcarbamates. (8), (9) and (10) through a regiospecific cyclisation of quinone imine intermediates.If the acylamino group is part of a ring, the yield of benzimidazoles (15) increases with the size of the lactam ring.The direction of ring closure may be controlled by electronic and steric factors.
