Water-soluble steroidal anaesthetics

With the aim of finding a water-soluble intravenous general anaesthetic we have examined a range of steroids carrying a basic substituent at the 11-position. Compounds with 11β-dialkylaminoacyloxy-or 11α-dialkylamino-substituents formed water-soluble salts that showed the desired activity in mice. The 11β-esters can be prepared via the corresponding 11β-haloacetoxy compounds. The 11α-dialkyl-amines can be prepared by reduction of 11-oximes and subsequent alkylation. Structure-activity studies have involved modification of the solubilising group, variation of substituents on ring A and at the 17-position and introduction of double bonds. 11α-Dimethylamino-2β-ethoxy-3α-hydroxy-5α-pregnan-20-one (minaxolone) forms salts that are readily soluble in water at physiologically acceptable pH to give stable solutions of high anaesthetic potency.