Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

Cancers are a large family of diseases that involve abnormal cell growth with the potential to invade or spread to other parts of the body. Cancer is the second cause of mortality after cardiac diseases in the world. It is continuing to act as a major problem of health in both developing and developed countries. Accordingly, the search for new anticancer agents is extremely desirable to improve survival rates and minimize toxicities and drug resistance.Many researchers reported the importance of pyrido[2,3-d]pyrimidine as an interesting bioactive scaffold implicated in the development of anticancer agents. Also, literature survey highlighted the apoptotic activity of certain pyrido[2,3-d]pyrimidines leading to their anticancer effect. Accordingly, this research focused on the synthesis of novel pyrido[2,3-d]pyrimidines hoping to obtain promising anticancer agents with fewer side effects.The present investigation deals with the synthesis of bicyclic derivatives, namely: (4-substituted phenyl)pyrido[2,3-d] pyrimidin-4-amine IVa-h, 7-(4-methoxyphenyl)-4-(phenylamino)5-(4-substituted phenyl)pyrido[2,3-d] pyrimidin-2(1H)-thione Va-d, 1-(7-(4-methoxyphenyl)-3-phenyl-5-(4-substituted phenyl)-2-thioxo-2,3-dihydro pyrido[2,3-d]pyrimidin-4-yl)-3-phenyl thiourea VIa-d, 5-(4-(methylthio) phenyl)-7-(4-(un)substitute dphenyl)-2-thioxo-2,3-dihydropyrido[2,3-d] pyrimidin-4(1H)-one VIIa-d, 2-hydrazinyl-5-(4-(methylthio) phenyl)-7-(4-(un)substituted phenyl)pyrido [2,3-d]pyrimidin-4(3H)-one VIIIa,b, in addition to tricyclic derivatives: 3-amino-6-(4-(methylthio)phenyl)-8-(4-(un)substituted phenyl)-pyrido[2,3-d] [1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one IXa,b ,6-(4-(methyl thio)phenyl)- vii 8-(4-(un)substituted phenyl)-3-thioxo-2,3-dihydropyrido[2,3-d][1,2,4] triazolo[4,3-a]pyrimidin-5(1H)-one Xa,b. Compounds IVa-h, Va-d, VIa-d, VIIa-d and VIIIa,b were evaluated for their anticancer activity as EGFR inhibitors, using Gefitinib as a reference compound

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