Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives.
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-furancarbo xamide 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 the light of these results, alfuzosin was selected for clinical evaluation.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D011799:Quinazolines / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D011799:Quinazolines; C047638:alfuzosin