Following identification of a virtual hit compound able to mimic interactions of the Hsp90 inhibitor geldanamycin within the Hsp90 ATP binding site, we have designed and synthesised a range of substituted 4‐aryldihydropyrimidinone‐5‐carboxylate derivatives (5a–n) for structure–activity relationship (SAR) study as Hsp90 inhibitors within human breast cancer cell models. The gene discussed is HSP90AA1; the disease is breast carcinoma.