الفهرس 
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Abstract
In this investigation, tetrahydropyrimidine derivatives were synthesized and utilized to achieve a variety of heterocycles of synthetic and pharmacological importance.
The original work of this thesis is presented in three parts:
Part I:
The building block synthon, 1-(4-(1,3-diphenyl-1H-pyrazol-4-yl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethan-1-one was efficiently synthesized by Biginelli reaction of 1,3-diphenyl-1H-pyrazole-4-carbaldehdye, acetylacetone, and thiourea, and submitted to react with ethyl chloroacetate and chloroacetyl chloride under different conditions to afford some N-heterocycles integrated with pyrazole scaffold. Hydrazinolysis of the pyrimidinethione was studied under different conditions. The insecticidal activity for these compounds, DFT calculations, and docking were run and discussed. Some of them exhibited 100% mortality against Nilaparvata lugens and Mythimna separata.
Part II:
Proclivity of tetrahydropyrimidinethione derivative encompassing 1,3-diphenylpyrazole moiety was studied toward some carbon electrophiles in an attempt to synthesize some heteroannulated compounds. Also, pyrimidine dimer and pyrimidinotriazepine derivative were obtained through reactions with 1,2-diaminoethane and 2-cyanoacetohydrazide, respectively. Oxidation of the starting pyrimidinethione was mainly dependent on the oxidizing agent used. The synthesized compounds were examined as antitumor agents against four human different cancer cell lines including hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3) and colon cancer (HCT-116). The results obtained revealed that some of them exhibited satisfactory activities.
Part III:
Tetrahydropyrimidinone derivative was synthesized through one-pot three components condensation of 1,3-diphenylpyrazole-4-carbaldehyde with pentan-2,4-dione and urea under Biginelli reaction conditions. The corresponding chloro and hydrazino derivatives were synthesized and utilized for the construction of some valuable N-heterocycles encompassing both pyrazole and pyrimidine cores, such as triazolopyrimidine, tetrazolopyrimidine, pyrazole, and pyrazolone derivatives through condensation with nitrogen nucleophiles and carbon electrophiles. The antiproliferative activity evaluation of the synthesized compounds against four human carcinoma cell lines namely, liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT-116) cell lines revealed that some of them provided significant potency, as well as the density-functional theory (DFT) was studied. The permeability of various hydrophilic and hydrophobic synthesized compounds across both normal and cancer cells is confirmed via DFT simulation in which the much higher permeability through aquaporin channels revealed the selective cytotoxicity toward cancer cells.