Patent Evaluation: Novel Tetralones as Potassium Channel Activators

Summary

Novelty: Novel tetralones are disclosed which are said to be potassium channel activators. These are potentially useful in the treatment of hypertension and asthma.

Biology: In vitro activity was determined by measuring the compounds' ability to inhibit noradrenaline-induced contractions of rat portal vein, and resting tension of guinea-pig trachea. In vivo activity was determined by measuring the reduction of blood-pressure in SHR rats. Data are given for twenty-four compounds. 1,2-Dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphthalene-6-carbonitrile had IC₅₀s of 0.6 and 0.1 μM, respectively, and produced a 97 mmHg decrease in blood pressure at 1 mg/kg po.

Chemistry: The syntheses of sixty-five examples and fifty-five intermediates are detailed. The compounds are prepared by the epoxidation of dihydronaphthalene-ones followed by amine-induced epoxide opening. Fourteen compounds are specifically claimed.

Structure: