الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
In The Present Work, Design And Synthesis Of Novel Diaryl Pyrazole Or 1,2,4-Triazole Bearing Either Carboxamide Or Uredio Or 1,3,4-Oxadiazole Heterocyclic Derivatives Viia-F, Xia-F, Xvia-E, Xxia-F And Xxiia-D Have Been Discussed. The Chemical Structures Of The New Compounds Were characterized Using Spectral And Elemental Analyses. The Newly Synthesized Compounds Were Evaluated For Their In Vivo Anti-Inflammatory/Analgesic Activities Compared To Celecoxib. In Addition To, Coxs And Seh Inhibitory Assay Relative To Celecoxib And AUDA. Finally, Docking Studies Were Performed For Certain Compounds To Strengthen Our Rational.
This Thesis Consists Of The Following Parts:
1- Introduction:
In This Section, The Inflammatory Process And Its Main Pathways Which Were Targeted As Anti-Inflammatory Were Discussed.
2- Aim Of The Work:
This Part Discussed The Research Rationale And The Major Aims That Guided The Theoretical And Practical Work.
3- Discussion:
This Section Illustrated The Different Experimental Methods That Could Be Used For The Synthesis Of The Designed Compounds With Summarized Data About Their characterization.
4- Experimental:
This Part Clarifies The Practical Procedures Of The Reported, The New Intermediate And Final Compounds. Additionally, The Spectral And Elemental Microanalytical Data Of The New Compounds Were Accentuated.
The Following Compounds Are Prepared
Reported Compounds ( 9 Compounds)
Ethyl 2,4-Dioxo-4-Phenylbutanoate (II)
4-Hydrazinylbenzenesulfonamide Hydrochloride (IV)
Ethyl 5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxylate (V)
5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxylic Acid (VI)
Benzoylglycine (XIII)
2-Phenyloxazol-5(4H)-One (XIV)
4-(2-(5-Oxo-2-Phenyloxazol-4(5H)-Ylidene)Hydrazinyl)Benzenesulfonamide (XV)
Methyl 5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carboxylate (XVII)
4-(3-Hydrazinyl-5-Phenyl-1H-1,2,4-Triazol-1-Yl)Benzenesulfonamide (XVIII)
New Intermediates (5 Compounds):
4-(3-(Hydrazinecarbonyl)-5-Phenyl-1H-Pyrazol-1-Yl)Benzenesulfonamide (VIII)
5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carbonyl Azide (IX)
4-(3-Isocyanato-5-Phenyl-1H-Pyrazol-1-Yl)Benzenesulfonamide (X)
5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carbonyl Azide (XIX)
4-(3-Isocyanato-5-Phenyl-1H-1,2,4-Triazol-1-Yl)Benzenesulfonamide (XX)
New Final Compounds (27 Compounds):
N-Cyclohexyl-5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxamide (Viia)
4-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxamido)Butanoic Acid (Viib)
N-Adamantyl-5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxamide (Viic)
Ethyl 1-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carbonyl)Piperidine-4-Carboxylate (Viid)
5-Phenyl-1-(4-Sulfamoylphenyl)-N-(4-(Trifluoromethyl)Phenyl)-1H-Pyrazole-3-Carboxamide (Viie)
11-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazole-3-Carboxamido)Undecanoic Acid (Viif)
4-(3-(3-Cyclohexylureido)-5-Phenyl-1H-Pyrazol-1-Yl)Benzenesulfonamide (Xia)
4-(3-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazol-3-Yl)Ureido)Butanoic Acid (Xib)
4-(3-(3-Adamantylureido)-5-Phenyl-1H-Pyrazol-1-Yl)Benzenesulfonamide (Xic)
Ethyl 1-((5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazol-3-Yl)Carbamoyl)Piperidine-4-Carboxylate (Xid)
4-(5-Phenyl-3-(3-(4-(Trifluoromethyl)Phenyl)Ureido)-1H-Pyrazol-1-Yl)Benzenesulfonamide (Xie)
11-(3-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-Pyrazol-3-Yl)Ureido)Undecanoic Acid (Xif)
4-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carboxamido)Butanoic Acid (Xvia)
N-Adamantyl-5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carboxamide (Xvib)
Ethyl 1-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carbonyl)Piperidine-4-Carboxylate (Xvic)
5-Phenyl-1-(4-Sulfamoylphenyl)-N-(4-(Trifluoromethyl)Phenyl)-1H-1,2,4-Triazole-3-Carboxamide (Xvid)
11-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazole-3-Carboxamido)Undecanoic Acid (Xvie)
4-(3-(3-Cyclohexylureido)-5-Phenyl-1H-1,2,4-Triazol-1-Yl)Benzenesulfonamide (Xxia)
4-(3-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazol-3-Yl)Ureido)Butanoic Acid (Xxib)
4-(3-(3-Cyclohexylureido)-5-Phenyl-1H-1,2,4-Triazol-1-Yl)Benzenesulfonamide (Xxic)
Ethyl 1-((5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazol-3-Yl)Carbamoyl)Piperidine-4-Carboxylate (Xxid)
4-(5-Phenyl-3-(3-(4-(Trifluoromethyl)Phenyl)Ureido)-1H-1,2,4-Triazol-1-Yl)Benzenesulfonamide (Xxie)
11-(3-(5-Phenyl-1-(4-Sulfamoylphenyl)-1H-1,2,4-Triazol-3-Yl)Ureido)Undecanoic Acid (Xxif)
4-(3-(5-((Adamantan-1-Yl)-1,3,4-Oxadiazol-2-Yl)-1-Phenyl-1H-Pyrazol-5-Yl)Benzenesulfonamide (Xxiia)
4-(3-(5-(Adamantan-1-Yl)-1,3,4-Oxadiazol-2-Yl)-1-Phenyl-1H-1,2,4-Triazol-5-Yl)Benzenesulfonamide (Xxiib)
4-(1-Phenyl-3-(5-(4-(Trifluoromethyl)Phenyl)-1,3,4-Oxadiazol-2-Yl)-1H-Pyrazol-5-Yl)Benzenesulfonamide (Xxiic)
4-(1-Phenyl-3-(5-(4-(Trifluoromethyl)Phenyl)-1,3,4-Oxadiazol-2-Yl)-1H-1,2,4-Triazol-5-Yl)Benzenesulfonamide (Xxiid)
5- Pharmacological Screening:
This Section Showed The Methods And The Results Used For In Vivo And In Vitro Pharmacological Evaluation Of The Final Synthesized Compounds. It Included:
A- Anti-Inflammatory Screening:
The Anti-Inflammatory Activity Of The Newly Synthesized Compounds Was Evaluated Using ”Rat Paw Carrageenan Edema” Method. Ten Compounds Viic, Viie, Xia, Xic, Xie, Xvib, Xvid, Xxia And Xxic Showed Good To Excellent Anti-Inflammatory Activity (84.19-98.15% Edema Inhibition) Compared To The Reference Standard, Celecoxib.
B- Analgesic Screening:
All New Compounds Were Evaluated For Their Analgesic Activity Using ”Acetic Acid-Induced Writhing Test”. Four Compounds Viic, Xie, Xxic And Xxie Possessed Good Activity (50.00-65.67% Writhing Inhibition) Compared To The Reference Drug, Celecoxib.
C- In Vitro Inhibition Of COX-2/Seh:
All New Compounds Were Evaluated For Their In Vitro Inhibition Of COX-2/Seh Using Enzyme Immunoassay Kits from Cayman Chemical Company (Catalogue Number 701070 And 701080, Cayman Chemical, Ann Arbor, MI, USA) For COX-2 And Using A Cell-Based Assay System Of 96-Well Format For Seh. Two Compounds Showed The Highest Inhibitory Activity Against Both COX-2 (IC50 = 1.24 And 1.85 Μm; SI = 7.03 And 6.41, Respectively) And Seh (IC50 = 0.4 And 0.55 Nm, Respectively) In Comparison To Celecoxib And AUDA.
D- Cardiovascular Evaluation:
The Cardiovascular Evaluation Of The Most Effective Compounds Was Tested Through Inhibition Of Both Seh And COX-2 Isoenzymes, where The Evaluated Compounds Showed A Good Protective Ability Against The COX-2 Inhibitors Associated With Cardiovascular Disorders.
6- Molecular Docking:
Molecular Modelling Studies Were Performed Using Molecular Operating Environment (MOE) Version 2008 Software. The Most Active In Vivo Compounds Were Docked Into Both COX-2 And Seh Iso-Enzymes To Rationalize The Biological Results.
7- References:
This Part Includes 257 References Covering The Period from 1853 To 2019.