N2-(4-Substituted-2,6-dichlorophenyl)-N1,N1-dimethylformamidines as antihypertensive and diuretic agents

Abstract

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.

PONy Dyes: Direct Addition of P(III) Nucleophiles to Organic Fluorophores

“…4-(dimethylamino)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde 1,4-Dioxane (25 mL) was added to the solid 2-bromo-4-(dimethylamino)benzaldehyde [15] (684 mg, 3.0 mmol), bis(pinacolato)diboron (840 mg, 3.3 mmol), KOAc (880 mg, 9.0 mmol) and Pd(dppf)Cl2 (66 mg, 0.09 mmol), the mixture was deoxygenated on a Schlenk line and stirred under N2 at 90 °C (bath temperature) for 4 h. Upon cooling to rt, the reaction mixture was filtered through a 1.5 cm pad of Celite washing with EtOAc (100 mL). The filtrate was evaporated; the residue was dissolved in DCM and applied onto a column with 30 g SiO2.…”