Dihydrofolate reductase (DHFR) inhibitors have proved to be of value as antibacterial, antimalarial, and antitumor agents. Some 2,4-diamino-5-methyl-6-[(substituted anilino)methyl]pyrrido[2,3-d]pyrimidines were reported earlier as DHFR inhibitors. Using non-parabolic Hansch models, a QSAR study was performed in an attempt to find out the required physicochemical and structural features of these compounds for DHFR inhibition. This study revealed the importance of resonance effect at R2 and R3

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... itions and sum of molar refractivity (MR) at R2, R3, R4, and R5 positions of the ring C. Lipophilicity of the whole molecule (log P) also played an important role. The presence of OCH 3 group at R4 of the phenyl C ring and CH 3 at R1 of anilino N might be advantageous to DHFR inhibition. This QSAR study is beneficial for future studies to carry out further tailoring of this type of compounds with an objective to increase DHFR inhibitory activity.