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Der Pharmacia Sinica
ISSN: 0976-8688
Eurosc i con Conference on
Medicinal Chemistry
and Biosimilars
M a r c h 2 5 - 2 6 , 2 0 1 9
B u d a p e s t , H u n g a r y
Medicinal Chemistry & Biosimilars 2019
A
novel series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine derivatives was
successfully designed, synthesized and evaluated as new chemical
scaffold with vascular endothelial growth factor receptor VEGFR 2 inhibitory
activity. Compounds 6c and 6b showed enzyme inhibition of 97% and
87% respectively and they also exhibited potent dose related VEGFR 2
inhibition with IC50 value 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 protocols of molecular modelling, prior to their synthesis and
biological evaluation. First, Sorafenib was docked in the binding site of VEGFR
2 to study its binding orientation and affinity, followed by generation of valid
3D QSAR pharmacophore model to be implemented in virtual screening of 3D
databases. Structures with promising results of pharmacophore based virtual
screening were refined using molecular docking studies into the binding site of
VEGFR 2. Design of the novel scaffold was accomplished adopting the results
of pharmacophore model generation and molecular docking studies. Different
derivatives with the novel scaffold were validated using docking studies and
pharmacophore mapping where they exhibited promising results as VEGFR
2 inhibitors to be synthesised and biologically evaluated.6,7-dihydro-5H-
cyclopenta[d]pyrimidine is a new scaffold that can be further optimized for
synthesis of promising VEGFR 2 inhibitors.
Biography
Nahla A H Farag is a Professor of Pharmaceutical Medicinal
Chemistry, Head of department, Faculty of Pharmacy at Misr
International University (MIU), Cairo, Egypt since 2015. She has
completed PhD in Pharmaceutical Medicinal Chemistry from
Faculty of Pharmacy, Cairo University, Cairo, Egypt in 2001. She
has established a new course in computer aided drug design
for senior undergraduate students in MIU since 2013 till now.
She has also established a Drug Design Center with highly
advanced computer labs and high trained teaching assistant
team for post graduate and undergraduate teaching course
and workshops for advanced researches inmolecular modeling
techniques.
nahla.farag@miuegypt.edu.eg3D-QSAR pharmacophore modeling, virtual screening and
docking studies for lead discovery of novel scaffold for VEGFR
2 inhibitors: design, synthesis and biological evaluation
Nahla A Farag
1
, Mahitab K Sobhy
1
, Samar Mowafy
1
, Deena S
Lasheen
2
and Khaled A M Abouzid
2
1
Misr International University, Egypt
2
Ain Shams University, Egypt
Nahla A Farag et al., Der Pharmacia Sinica 2019, Volume:10
DOI: 10.21767/0976-8688-C1-003