Pyrimidine derivatives. 4. Synthesis and antihypertensive activity of 4-amino-2-(4-cinnamoylpiperazino)-6,7-dimethoxyquinazoline derivatives.
A series of 30 4-amino-2-(4-cinnamoylpiperazino)-6,7-dimethoxyquinazoline derivatives was prepared and tested for their ability to reduce blood pressure in conscious, spontaneously hypertensive rates (SHR). A number of these compounds, notably 4-amino-2-(4-cinnamoylpiperazino)-6,7-dimethoxyquinazolines 3a (R1 = H; R2 = Ph), 3j (R1 = H; R2 = 4-EtOPh), and 5a (R1 = H; R2 = 2-furyl), showed activity at oral doses of 0.3-10 mg/kg. The effects of the 4-substituents of the piperazino group on activity are discussed. Compounds 3a, 3j, and 5a were effective in renal hypertensive rats at oral doses of 3 and 10 mg/kg and showed alpha-adrenoceptor blocking effects in isolated aortas of rats. A 5-day consecutive oral administration of 3a and 3j in SHR did not lead to development of tolerance.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011743:Pyrimidines; D011799:Quinazolines