Patent Evaluation: Imidazoline Derivatives as Stimulators of Insulin Secretion

Summary

Novelty: The (—) enantiomer of efaroxan and a method for its purification from the racemic mixture, are claimed. The compound is said to stimulate insulin secretion without affecting the undesirable antagonism of α₂-adrenoreceptors, which is associated with the racemic mixture.

Biology: Data are presented for the evaluation of efaroxan enantiomers and racemic derivatives on rat islet and vas deferens tissue. Both (—) and (+) enantiomers of isopropyl efaroxan (100 μM) reversed inhibition of insulin secretion which was initiated by the K⁺ channel activator, diazoxide (250 μM). Only the (—) isomer of efaroxan reversed inhibition by diazoxide; moreover it did not show the α₂-adrenoreceptor antagonism associated with (+) efaroxan.

Chemistry: The (—) enantiomer of 2-[2-(2-ethyl-2,3-dihydobenzofuranyl)]-2-imidazoline (efaroxan) is specifically claimed. Details are given for the purification of efaroxan and isopropyl efaroxan enantiomers by standard crystallization techniques.

Structure: