Thesis abstract The present investigation is concerned with the synthesis and biological activities of a new series of pyrimidine derivatives. The starting pyrimidine derivative I was obtained from the reaction of trimethoxy benzaldehyde, ethyl cyanoacetate and N-allyl thiourea in ethanol containing potassium carbonate under reflux. S-alkylation of compound I with alkyl halides or substituted chloroacetanilides derivatives gave compounds IIa-g. Reaction of compound IIa with different amines afforded compounds IIIa-c. Also, hydrazinolysis of compound IIa yielded the hydrazino compound IV. (Scheme 1) In an attempt to synthesize pyrazoline derivatives VIIa,b and VIIIa-g, chalcones Va-i were prepared using different acetophenone and aromatic aldehyde derivatives. Aminolysis of compound IIa with the chalcones Va,b followed by cyclocondensation using hydrazine hydrate led to the formation of the pyrazolines VIIa,b. On the other hand, the pyrazolines VIIIa-g were obtained by condensation of the hydrazino derivative IV with the appropriate chalcones Vc-i in ethanol under reflux. (Scheme 2) In addition, refluxing hydrazino compound IV with either ethyl acetoacetate or acetylacetone in ethanol/acetic acid gave the pyrazole derivative IX or X respectively. Furthermore, the hydrazino derivative IV underwent cyclocondensation with 2,5-hexanedione to afford the 2,5-dimethyl-1H-pyrrole derivative XI. (Scheme 3) Moreover, condensation of the hydrazino compound IV with appropriate aromatic aldehyde derivatives, maleic anhydride, isatine and dimedone led to compounds XIIa-f, XIII, XIV and XV respectively. (Scheme 4) Tetrazolo-pyrimidine derivative XVI was obtained from the reaction of hydrazino derivative IV with nitrous acid. On the other hand, triazolo-pyrimidines XVII, XIXa-c and XX were obtained by the reaction of IV with formic acid, aromatic acid chlorides and carbon disulphide. However,pyrimido-triazines XXI and XXII were be afforded via the cyclization of the key compound IV with 4-methoxyphenacylbromide and pyruvic acid respectively. (Scheme 5) Furthermore, theoretical discussion and detailed survey for the experimental results attained with interpretation of data. The chemical structure of the newely synthesized compounds was confirmed by IR, 1HNMR, 13CNMR, mass spectrometry and elemental analysis. Some of the newly synthesized heterocycles were evaluated for their antimicrobial and anticancer activities. Considering antimicrobial activity, it was observed that most of the targets exhibited broad spectrum activity. However, compounds IIf, XIIe and XIXa represented the highest potency compared to the reference drugs Ampicillin, Gentamycin and Gemifloxacin as antibacterial agents and Amphotericin B as antifungal agent. On the other hand, compound IId showed excellent antibacterial activity against gram positive and gram negative bacterial strains. On the other hand, the anticancer activity showed that some of the selected compounds having promising anticancer activity against colon and breast carcinoma cell lines compared to reference drug Doxorubcin. The most potent cytotoxic compound was hydrazino derivative IV with (IC50 =3.87 µg/ml, 4.37 µg/ml) against breast and colon carcinoma cell lines. On the contrary, compound XIIa exhibited moderate activity against colon carcinoma cell line with (IC50 =6.71 µg/ml). However, compounds XVI and XIXc have the least activity against the two cell lines. On the other hand, IV and XIIa compounds have the high cytotoxic activity against two cell lines indicating the importance of hydrazino and trimethoxy groups.