الفهرس 
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Abstract
Title: Design And Synthesis Of New Aza-Heterocyclic Compounds With Potential Biological Activity.
Keywords: Imidazo[1,2-A]Pyridine, Anti-Inflammatory, selective COX-2 Inhibition, Anticancer Activity, Cytotoxicity, EGFR Inhibition.
In The Present Study, Eight New Series Of Imidazo[1,2-A]Pyridines Viiia-D, Ixa-D, Xa-D, Xia-D, Xiia-F, Xiva-C, Xva-D And Xviia-D Were Designed And Synthesized. characterization Of The Chemical Structures Of These New Compounds Was Performed Using Spectral And Elemental Analyses. Three Series Viiia-D, Ixa-D And Xa-D Were Tested For Their In Vitro COX-1/COX-2 Isozymes Inhibitory Activity And In Vivo Anti-Inflammatory Activity. Also, The Most Potent Anti-Inflammatory Compounds Ixa, Ixd, Xc And Xd Were Subjected To Ulcerogenic Liability And Histopathological Examinations. In Addition, The Other Five Series Xia-D, Xiia-F, Xiva-C, Xva-D And Xviia-D Were Chosen By The National Cancer Institute (NCI), Bethesda, Maryland, USA For Antitumor Screening. The Obtained Screening Results Of All The Newly Synthesized Compounds Were Demonstrated As A Percent Of Growth Inhibition (GI%). The Most Broadly Active Compounds Xib, Xic, Xiie And Xiif In Antitumor Screening Were selected And Evaluated For Their Cytotoxic Activity Against Leukemia K-562 Cancer Cell Line Using The MTT Cytotoxicity Assay. Also, The Previous Compounds Were Further Tested For Their EGFR Inhibitory Activity. The Most Active Antitumor Compound Xic Was selected For Further Study Regarding Its Effect On Cell Cycle Progression And Induction Of Apoptosis In The K-562 Cell Line. Then Compound Xic Was Chosen To Determine Its Ability To Induce Activation Of Caspase-3 To Find A Possible Mechanism For Its Antiproliferative Activity. Finally, Molecular Docking Was Performed For The Prepared Compounds To Support The Biological Results.
This Thesis Consists Of The Following Parts:
1- Introduction:
In This Chapter, A Brief Literature Review Presented Imidazo[1,2-A]Pyridine Nucleus And Different Pharmacological Activities Of Some Imidazo[1,2-A]Pyridine Derivatives.
2- Aim And Work:
It Included The Research Objectives And Rationale Upon Which The Newly Synthesized Compounds Were Designed.
3- Results And Discussion:
In This Part, Theoretical Bases Of The Experimental Methods And The Conditions Of The Reactions Adopted For The Prepared Compounds Were Discussed. In Addition, It Dealt With The Confirmation Of The Newly Synthesized Compounds By Different Methods Including Infrared, Mass, 1H NMR And 13C NMR Spectra. In Addition, This Part Showed The Results And Discussion Of Pharmacological Evaluation Of The Desired Synthesized Compounds.
4- Experimental Protocols:
This Part Presented The Practical Procedures Used For The Synthesis Of The Reported Compounds And New Final Compounds. Also, It Summarized Their Spectral And Microanalytical Data. In Addition, It Showed The Methods Used For In Vitro And In Vivo Pharmacological Evaluation As Well As Molecular Docking Of The Finally Synthesized Compounds.
Synthesis Of The Following Intermediates Was Found To Be Essential For Our Study
Reported Compounds:
1- P-Methylsulfonylacetophenone (III).
2- 2-Bromo-1-(4-(Methylsulfonyl)Phenyl)Ethan-1-One (IV).
3- 2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridine (VI).
4- 2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridine-3-Carbaldehyde (VII).
5- N-Phenylhydrazinecarbothioamide (Xiiia).
6- N-(P-Tolyl)Hydrazinecarbothioamide (Xiiib).
7- N-(4-Chlorophenyl)Hydrazinecarbothioamide (Xiiic).
8- (E)-2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methylene) Hydrazine-1-Carbothioamide (XVI).
Newly Synthesized Compounds:
This Work Includes 33 New Compounds Classified Into Eight Series.
The First Series Includes:
(E)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-1-Phenylprop-2-En-1-One (Viiia).
(E)-1-(4-Methoxyphenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Prop-2-En-1-One (Viiib).
(E)-1-(4-Chlorophenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Prop-2-En-1-One (Viiic).
(E)-1-(4-Bromophenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Prop-2-En-1-One (Viiid).
The Second Series Includes:
2-(4-(Methylsulfonyl)Phenyl)-3-(3-Phenyl-4,5-Dihydro-1H-Pyrazol-5-Yl)Imidazo [1,2-A]Pyridine (Ixa).
3-(3-(4-Methoxyphenyl)-4,5-Dihydro-1H-Pyrazol-5-Yl)-2-(4-(Methylsulfonyl) Phenyl)Imidazo[1,2-A]Pyridine (Ixb).
3-(3-(4-Chlorophenyl)-4,5-Dihydro-1H-Pyrazol-5-Yl)-2-(4-(Methylsulfonyl) Phenyl)Imidazo[1,2-A]Pyridine (Ixc).
3-(3-(4-Bromophenyl)-4,5-Dihydro-1H-Pyrazol-5-Yl)-2-(4-(Methylsulfonyl) Phenyl)Imidazo[1,2-A]Pyridine (Ixd).
The Third Series Includes:
(1E,2E)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-1-Phenyl Prop-2-En-1-One Oxime (Xa).
(1E,2E)-1-(4-Methoxyphenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridin-3-Yl)Prop-2-En-1-One Oxime (Xb).
(1E,2E)-1-(4-Chlorophenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridin-3-Yl)Prop-2-En-1-One Oxime (Xc).
(1E,2E)-1-(4-Bromophenyl)-3-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridin-3-Yl)Prop-2-En-1-One Oxime (Xd).
The Fourth Series Includes:
(E)-2-(4-(Methylsulfonyl)Phenyl)-3-((2-Phenylhydrazono)Methyl)Imidazo[1,2-A]Pyridine (Xia).
(E)-2-(4-(Methylsulfonyl)Phenyl)-3-((2-(P-Tolyl)Hydrazono)Methyl)Imidazo[1,2-A]Pyridine (Xib).
(E)-3-((2-(4-Methoxyphenyl)Hydrazono)Methyl)-2-(4-(Methylsulfonyl)Phenyl) Imidazo[1,2-A]Pyridine (Xic).
(E)-3-((2-(4-Chlorophenyl)Hydrazono)Methyl)-2-(4-(Methylsulfonyl)Phenyl) Imidazo[1,2-A]Pyridine (Xid).
The Fifth Series Includes:
(E)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-N-Phenyl Methanimine (Xiia).
(E)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-N-(P-Tolyl) Methanimine (Xiib).
(E)-N-(4-Methoxyphenyl)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridine-3-Yl)Methanimine (Xiic).
(E)-N-(4-Fluorophenyl)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methanimine (Xiid).
(E)-N-(4-Chlorophenyl)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methanimine (Xiie).
(E)-N-(4-Bromophenyl)-1-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methanimine (Xiif).
The Sixth Series Includes:
(E)-2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methylene)-N-Phenylhydrazine-1-Carbothioamide (Xiva).
(E)-2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methylene)-N-(P-Tolyl)Hydrazine-1-Carbothioamide (Xivb).
(E)-N-(4-Chlorophenyl)-2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methylene)Hydrazine-1-Carbothioamide (Xivc).
The Seventh Series Includes:
2-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-1H-Benzo[D] Imidazole (Xva).
5-Methyl-2-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-1H-Benzo[D]Imidazole (Xvb).
5-Chloro-2-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-1H-Benzo[D]Imidazole (Xvc).
2-(2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)-5-Nitro-1H-Benzo[D]Imidazole (Xvd).
The Eighth Series Includes:
(E)-2-(2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A]Pyridin-3-Yl)Methylene) Hydrazinyl)-4-Phenylthiazole (Xviia).
(E)-4-(4-Methoxyphenyl)-2-(2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridine-3-Yl)Methylene)Hydrazinyl)Thiazole (Xviib).
(E)-4-(4-Chlorophenyl)-2-(2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridin-3-Yl)Methylene)Hydrazinyl)Thiazole (Xviic).
(E)-4-(4-Bromophenyl)-2-(2-((2-(4-(Methylsulfonyl)Phenyl)Imidazo[1,2-A] Pyridin-3-Yl)Methylene)Hydrazinyl)Thiazole (Xviid).
5- Molecular Docking Study:
This Part Showed The Results Of The Docking Study Of The Most Active Compounds.
6- Conclusion:
This Section Briefly Concluded Our Findings And The Most Important Results.
7- References:
This Part Included 185 References Between The Years 1970 To 2022.
8- Arabic Summary.