Microwave-Assisted Synthesis of Potential Bioactive Benzo-, Pyrido- or Pyrazino-thieno[3,2-<i>d</i>]pyrimidin-4-amine Analogs of MPC-6827

Abstract

Efficient microwave-assisted chemical processes were applied to the synthesis of an array of novel N-(4-methoxyphenylamino)-2-methyl benzo-, pyrido- or pyrazino-thieno[3,2-d]pyrimidin-4-amine derivatives. These heteroaromatic systems were envisioned as potent bioisosteric analogues of MPC-6827, an anticancer agent previously developed until phase II clinical studies. A brief evaluation and comparison of their antiproliferative activity on HT-29 and Caco-2, two human colorectal cancer cell lines, were also reported. At the tested concentrations (5 and 10 µM), thieno[3,2-d]pyrimidin-4-amines 4a and 4c exhibited an inhibitory effect similar to MPC-6827 on human colorectal cancer cell proliferation.

Keywords

• microwave-assisted chemistry
• thieno[3,2-<i>d</i>]pyrimidines
• colorectal cancer
• HT-29 cells
• caco-2 cells
• antiproliferative activity