Ahmad Basim

 
i
Synthesis and Identification of New Aminoacetylenic
Tetrahydrophthalimide Derivatives
Anticipated as COXs Inhibitor
By
Ahmed Basim
Thesis Submitted in Partial Fulfillment of the Requirements for the
Master Degree in Pharmaceutical Sciences at
University of Petra
Faculty of Pharmacy and Medical Sciences
Amman-Jordan
April 2014
ii
Synthesis and Identification of New Aminoacetylenic
Tetrahydrophthalimide Derivatives
Anticipated as COXs Inhibitor
By
Ahmed Basim
Thesis Submitted in Partial Fulfillment of the Requirements for the
Master Degree in Pharmaceutical Sciences at
University of Petra
Faculty of Pharmacy and Medical Sciences
Amman-Jordan
April 2014
 
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Abstract
Synthesis and Identification of New Aminoacetylenic
Tetrahydrophthalimide Derivatives
Anticipated as COXs Inhibitor
By
Ahmed Basim
University of Petra
April 2014
Supervisor Co-Supervisor
Prof. Zuhair Muhi-eldeen Prof. Tawfiq Arafat
Aminoacetylenic Tetrahydrophthalimide derivatives were synthesized from the
reaction of cis-1,2,3,6 Tetrahydrophthalimide with 3-bromoprop-1yne to generate
2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione (AM). A
mixture of 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione,
paraformaldehyde, cyclic amine and cuprous chloride in catalytic amount, in
peroxide free dioxane through mannich reaction yielded the desired
Aminoacetylenic compounds AM1-AM6. The IR, 1H-NMR, DSC, and elemental
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analysis were consistent with the assigned structures. The design of these
compounds as COX inhibitors is based on our rationalization for the important
criteria
Needed to overlap effectively with COX to induce antagonistic activity. These
criteria are: A) A basic amino group for ionic interaction. B) The aceltylenic group
for electrostatic interaction. C) The 2-butyne provides the appropriate distance
between the basic nitrogen and cis-1,2,3,6 Tetrahydrophthalimide. The docking
results show that all the designed compounds have good COX inhibition
especially AM4 had (-8.6 kcal/mol) for COX2 showing a promising approach in
managing inflammatory diseases.
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Acknowledgments
Hereby I dedicate my thesis to a great man that I have seen none like him, the
one who taught me the meaning of dedication, commitment and sacrifice, my role
model that I’ll always look up to, to my beloved father, I owe you an eternal
gratitude.
To my mother: to immortalize her smiles, tears, kindness and unconditional love.
Many thanks for two great brothers Atheer and Ayad, for that their consultations
were always of a great deal of help.
Thanks to my dear friend Ragheed for setting clear path for me to follow and
making things easier.
I am so grateful for Ibrahim AKA: bebo, bay_bow, beez, beepzone, darabeez for
that he got us rid of the sodium with the new procedure.
Special thanks to Ubisoft®, sony®, Eiichiro Oda, Masashi Kishimoto, mohammed
rudha and Ahmed Issam for the great mental support.
Many thanks for the Petra Uni. staff especially: Prof.zuhair Muhi-eldeen, Prof.
Tawfiq Arafat, dr.kenza mansoor, dr.nidhal Al-Qinna and Dr.Ghadeer Suaifan for
their support and Jordan university staff who helped through the analysis
especially: Ayad, Omran And Rula.
Sincere gratitude to Sir Thomas Edison, Robert E. Khan, Vint Cerf, Isidor Rabi,
Dr.Ali Al-wardy, Michael Faraday, Nikola Tesla, Larry page and Sergey Brim.
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And finally I want to thank me, myself and my fellow Ahmed Basim for their
extraordinary patience with me