N2-(4-Substituted-2,6-dichlorophenyl)-N1,N1-dimethylformamidines as antihypertensive and diuretic agents.
The synthesis of a series of N2-[4-[(arylmethyl)amino]-2, 6-dichlorophenyl]-N1,N1-dimethylformamidines that caused marked blood pressure lowering and/or diuresis in spontaneously hypertensive rats (SHR) is reported. Diuretic activity was not always associated with acute antihypertensive activity. Central nervous system effects, most notably sedation, were observed. Compound 9d, which lowered arterial blood pressure 37 mmHg in SHR when dosed at 100 mg/kg, was further evaluated in chronic hypertensive dogs because of apparent minimal CNS effects. A reduction in arterial blood pressure of 32 mmHg at 1.0 mg/kg during a 6-h postdosing interval was observed. This response was unrelated to alpha- or beta-adrenergic blockade, angiotensin I antagonism, or neuronal or ganglionic blockade. CNS effects were also observed.
D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002722:Chlorobenzenes / Q000138:chemical synthesis / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000652:urine; D013329:Structure-Activity Relationship
D000578:Amidines; D000959:Antihypertensive Agents; D002722:Chlorobenzenes; D004232:Diuretics; D007202:Indicators and Reagents; D012964:Sodium; D011188:Potassium