Trequinsin, a potent new antihypertensive vasodilator in the series of 2-(arylimino)-3-alkyl-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-py rim ido [6,1-a]isoquinolin-4-ones.
Series of 3-substituted-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido [6,1-a]isoquinoline-2,4-diones and 2-substituted-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-ones were synthesized and tested for blood pressure lowering properties in anesthetized normotensive cats and conscious spontaneously hypertensive rats. Several compounds in the 2-(arylamino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-one series display a high order of activity. The most active compounds are the alkyl derivatives of the 2-mesitylamino/2-mesitylimino tautomeric forms. The 2-(mesitylimino)-3-methyl analogue trequinsin is a potent antihypertensive agent and displays a hemodynamic profile characteristic of an arteriolar dilator. It is also a potent inhibitor of both cAMP phosphodiesterase and platelet aggregation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; C035964:trequinsin; D011433:Propranolol; D010646:Phentolamine