Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives

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Abstract
A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential .alpha.1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral .alpha.1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. In light of these results, alfuzosin was selected for clinical evaluation.