1153357-90-4

Upstream product

• 100-01-6 4-nitro-aniline 
• 71026-66-9 N-(tert-butoxycarbonyl)-1,4-phenylenediamine 
• 1445768-11-5 C₁₉H₂₂ClN₃O₃ 
• 106-50-3 1,4-phenylenediamine 
• 28479-22-3 2-chloro-4-isocyanato-1-methylbenzene 

Downstream Products

• 1437304-79-4 1-(3-chloro-4-methylphenyl)-3-{4-[(4-hydroxy-8-nitroquinazolin-5-yl)amino]phenyl}urea 

Relevant academic research and scientific papers

3D-QSAR pharmacophore modelling, virtual screening and docking studies for lead discovery of a novel scaffold for VEGFR 2 inhibitors: Design, synthesis and biological evaluation

A series of novel 6,7-dihydro-5H-cyclopenta[d]pyrimidine derivatives was successfully designed, synthesized and evaluated as a new chemical scaffold with vascular endothelial growth factor receptor (VEGFR 2) inhibitory activity. Compounds 6c and 6b showed enzyme inhibition of 97% and 87% at 10 μM, respectively, and exhibited potent dose-related VEGFR 2 inhibition with IC50 values of 0.85 μM and 2.26 μM, respectively. The design of the 6,7-dihydro-5H-cyclopenta[d]pyrimidine scaffold was implemented via consecutive molecular modelling protocols prior to the synthesis and biological evaluation of the derivatives. First, sorafenib was docked in the binding site of VEGFR 2 to study its binding orientation and affinity, followed by the generation of a valid 3D QSAR pharmacophore model for use in the virtual screening of different 3D databases. Structures with promising pharmacophore-based virtual screening results were refined using molecular docking studies in the binding site of VEGFR 2. A novel scaffold was designed by incorporating the results of the pharmacophore model generation and molecular docking studies. The new scaffold showed hydrophobic interactions with the kinase front pocket that may be attributed to increasing residence time in VEGFR 2, which is a key success factor for ligand optimization in drug discovery. Different derivatives of the novel scaffold were validated using docking studies and pharmacophore mapping, where they exhibited promising results as VEGFR 2 inhibitors to be synthesized and biologically evaluated. 6,7-dihydro-5H-cyclopenta[d]pyrimidine is a new scaffold that can be further optimized for the synthesis of promising VEGFR 2 inhibitors.

Design, synthesis and molecular modeling study of certain VEGFR-2 inhibitors based on thienopyrimidne scaffold as cancer targeting agents

Different series of novel thieno [2,3-d]pyrimidine derivative (9a-d,10a-f,l,m and 15a-m) were designed, synthesized and evaluated for their ability to in vitro inhibit VEGFR-2 enzyme. Also, the cytotoxicity of the final compounds was tested against a panel of 60 different human cancer cell lines by NCI. The VEGFR-2 enzyme inhibitory results revealed that compounds 10d, 15d and 15 g are among the most active inhibitors with IC50 values of 2.5, 5.48 and 2.27 μM respectively, while compound 10a remarkably showed the highest cell growth inhibition with mean growth inhibition (GI) percent of 31.57%. It exhibited broad spectrum anti-proliferative activity against several NCI cell lines specifically on human breast cancer (T7-47D) and renal cancer (A498) cell lines of 85.5% and 77.65% inhibition respectively. To investigate the mechanistic aspects underlying the activity, further biological studies like flow cytometry cell cycle together with caspase-3 colorimetric assays were carried on compound 10a. Flow cytometric analysis on both MCV-7 and PC-3 cancer cells revealed that it induced cell-cycle arrest in the G0-G1phase and reinforced apoptosis via activation of caspase-3. Furthermore, molecular modeling studies have been carried out to gain further understanding of the binding mode in the active site of VEGFR-2 enzyme and predict pharmacokinetic properties of all the synthesized inhibitors.

Novel 5-anilinoquinazoline-8-nitro derivatives as inhibitors of VEGFR-2 tyrosine kinase: Synthesis, biological evaluation and molecular docking

Vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibition is a well-established strategy to promptly tackle tumor growth by suppression of angiogenesis. We report herein a series of 5-anilinoquinazoline derivatives substituted by 1,3-disubstituted urea. All the newly synthesized compounds described were evaluated for VEGFR-2 kinase inhibition and antiproliferative activity against various cancer cells. The novel 1-aryl, 3-aryl-disubstituted urea quinazolines were effective VEGFR-2 kinase inhibitors with in vitro IC 50 values in the submicromolar range (compound 6f, IC50 12.0 nM), but showed a weak to moderate inhibitory activity on cancer cells. Molecular interactions of the compounds were studied using molecular docking studies. The Royal Society of Chemistry 2013.