A hitherto unreported impurity in Terazosin – elucidation of the structure, synthesis and cytotoxicity

Analysis of several batches of the a 1 –adrenergic blocking agent terazosin being used as a medication for treating benign prostatic hyperplasia and hypertension revealed the presence of a hitherto not reported impurity. The latter was isolated, and its structure was elucidated from NMR and Mass Spectrometry (MS) data and unambiguously confirmed by independent synthesis. This contamination, represented in 1-[4-(amino-6,7-dimethoxyquinazolin-2-yl)-piperazin-1-yl]-pentane-1,2-dione 2 is likely to occur as the product of a side-reaction in the catalytic hydrogenation step during the synthesis of the drug. Biological screening showed this compound as not cytotoxic for several human tumor cell lines and non-malignant fibroblasts.