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
 
iii
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 iv 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.
vi
And finally I want to thank me, myself and my fellow Ahmed Basim for their
extraordinary patience with me