Synthesis of Novel Amide Functionalized Pyrido[2,3-d]pyrimidine Derivatives and their Anticancer Activity

Abstract

A series of novel amide functionalized pyrido[2,3-d]pyrimidine derivatives were synthesized from 2-amino-6-(thiophen-2-yl)-4-(trifluoro-methyl)nicotinonitrile (1), which on reaction with trifluoroacetic acid to get pyridopyrimidine (2). Compound 2 when treated with bromoethyl acetate followed by hydrazine hydrate to get hydrazide derivatives 4. Compound 4 on reaction with different substituted aromatic aldehydes to obtain Schiff base derivatives 5a-f. In another way, compound 3 treated with different substituted amines and amino acids to obtain amide derivatives 6a-f, 7a-d and 8a-c. All the compounds evaluated for anti-cancer activity against four human cancer cell lines such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-prostate cancer (HTB-81) and HeLa-cervical cancer (CCL-2) and among the sythesized compounds, only 5d, 7d and 8a were identified as the potent compounds against the anticancer activity.