Synthesis and antiproliferative activity of imidazo[1,2-a]pyrimidine Mannich bases

• A series of 28 novel imidazo[1,2-a]pyrimidine Mannich bases have been synthesized.
• Library includes simple Mannich bases as well as 1,4-symmetrical dimers.
• Antiproliferative activity of 28 Mannich bases was evaluated against 3 cell lines.
• 5e, 6b, 7k exhibited excellent growth inhibitory activity comparable to doxorubicin.

A series of imidazo[1,2-a]pyrimidine Mannich bases were designed, synthesized in two phases. Mannich bases were obtained by one pot three component condensation of imidazo[1,2-a]pyrimidine with secondary amine or piperazine and excess of formaldehyde solution in methanol. The synthesized Mannich bases were screened for in vitro growth inhibition against a panel of 3 different human cancer cell lines. Most of the synthesized compounds exhibited antiproliferative activity with GI50 values ranging from 0.01 to 79.4 μM. Compounds 5e, 6b and 7k were found to be effective inhibitors of growth of all cell lines, with GI50 values similar to that of standard drug. The structure and activity relationship has been disclosed.

A series of 28 novel imidazo[1,2-a]pyrimidine Mannich bases have been designed, synthesized and their antiproliferative activity evaluated. Among them 5e, 6b, 7k were found to be potent with GI50 values similar to doxorubicin.Figure optionsDownload as PowerPoint slide