Patent Evaluation: Novel Potassium Channel Openers

Summary

Novelty: Methods for the enantiomer-selective preparation of (+)-N-(2-ethoxyphenyl)-N',N'-(1,2,2-trimethylpropyl)-2-nitroethene-1,1-diamine a known K⁺ channel antagonist and smooth muscle relaxant, are disclosed. The use of this enantiomer as an antihypertensive and anti-asthmatic agent forms a further part of the claim.

Biology: The superior potency of the (+) enantiomer was demonstrated by inhibition of K^+- induced contractions in rat aortic rings; the IC₅₀ value of the (+) enantiomer was 15.5 nM compared with 248.0 nM for the (-) enantiomer.

Chemistry: The preparative process comprizes the reaction of 1-[(1-ethoxy)phenylamino]-1-methylthio-2-nitroethene with 1,2,2-trimethylpropylamine in organic solvent at a temperature between 50-160°C to form the final product. Enantiomer-selectivity is achieved by either using a single enantiomer of the 1,2,2-trimethylpropylamine, or by employing sophisticated hplc methods. Two preparative examples are given. Methods for the preparation and use of N-(2-ethoxyphenyl)-N',N'-(1,2,2-trimethylpropyl)-2-nitroethene-1,1-diamine have been previously disclosed.

Structure: