This thesis describes the synthesis of new heterocyclic derivatives and evaluation of their biological activities. Chapter one: this chapter contains a brief literature review covering the most important biological activities and the general methods for synthesis of imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives. 5-Arylidene-3-phenethylimidazolidine-2,4-diones (IIIa-j) were synthesized according to scheme 1 via Knoevenagel condensation of 3-phenethylimidazolidine- 2,4-dione (II) with different aldehydes. According to scheme 2, the thiohydantoin derivatives (Va,b) were obtained by condensation of 2-thioxoimidazolidin-4-one (28) with appropriate aldehydes followed by NH alkylation with (2-bromoethyl) benzene. Synthesis of hydrazide intermediates VIIIa,b was achieved by hydrazinolysis of esters VIIa,b (scheme 3). Upon reaction of hydrazides VIIIa,b with carbon disulphide in ethanol in presence of potassium hydroxide afforded oxadiazole derivatives IXa,b. Condensation of the hydrazides VIIIa,b with appropriate aldehydes gave hydrazones Xa-c while, reaction with benzoylacetone produced 5- (4-chlorobenzylidene)-3-(2-(3-methyl-5-phenyl-1H-pyrazol-1-yl)-2-oxoethyl) imidazolidine-2,4-dione (XI) (scheme 3). Furthermore, the newely synthetized compounds were tested against virulence factors of Pseudomonas aeruginosa including protease, hemolysin, and pyocyanin. The imidazolidine-2,4-diones IIIc, IIIe, VIIIa and Xa showed complete inhibition of protease enzyme and almost completely inhibit the production of hemolysin. The x 2-thioxoimidazolidin-4-one derivative Va exhibited the best inhibitory activity against pyocyanin production. A docking study was preformed to explore potential binding interactions of the active compounds to quorum sensing receptors (LasR and RhlR) which are responsible for virulence genes expression. Chapter two: this chapter describes synthetic overview and pharmacological applications of thienopyridine derivatives (Schemes 4, 5, 6). Scheme 4 showed the hydrazinolysis of ester 92 to give the hydrazide XII which converted to oxadiazole derivative XIII by reaction with carbon disulphide. Alkylation of the oxadiazole XIII with different alkyl and aryl halides afforded the corresponding S-alkylated derivatives XIVa-d. Cyclization of acetohydrazide derivative XII with acetyl acetone and ethyl acetoacetate afforded the corresponding pyrazole derivatives XVa,b respectively (Scheme 4). Reaction of hydrazide XII with phenylisothiocyanate gave thiosemicarbazide derivative XVI which in turn, reacted with concentrated sulphuric acid to give thiadiazole derivative XVII. On the other hand, it reacted with sodium hydroxide to give triazole derivative XVIII (Scheme 5). Condensation of the hydrazide intermediate XII with appropriate aromatic aldehydes gave hydrazone derivatives XIX a-f (Scheme 6). Antimicrobial screening of the newly prepared compounds against gram positive, gram negative bacteria and fungal strains was performed. The results showed that some tested compounds exhibited a significant activity. The structure elucidation of new compounds was supported by elemental analyses, IR, 1HNMR, 13CNMR, in addition to mass spectrometry