Synthesis of quaternary ammonium salts of 16E-[4-(2-alkylaminoethoxy)-3-methoxybenzylidene]androstene derivatives as skeletal muscle relaxants

Synthesis of eighteen new quaternary ammonium salts of 16E-arylidene androstene derivatives as skeletal muscle relaxants is reported in the present study. The effects of possibly extended interonium distances on muscle relaxant activity are discussed. All the quaternary ammonium steroids produced reduction in the twitch responses, when screened for in vitro neuromuscular blocking activity using isolated chick biventer cervicis muscle preparation. However, the variable interonium distance, which is believed to range from 11 to 17 Å in these quaternary compounds and is associated with the built in flexibility of these structures about the single bonds on the moieties linked to ring D of the steroid skeleton, resulted in varied degrees of muscle relaxant activity. Some of the compounds also inhibited acetylcholinesterase activity in low concentrations so that they would not be directly suitable for use as muscle relaxants.

Graphical abstractA new series of quaternary ammonium salts of 16E-arylidene androstene derivatives with extended interonium distance has been synthesized and evaluated for skeletal muscle relaxant activity.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights▶ We synthesized eighteen new quaternary ammonium salts of 16E-arylidene androstene derivatives as skeletal muscle relaxants. ▶ All new quaternary ammonium steroids produced reduction in the twitch responses of isolated chick biventer cervicis muscle preparation. ▶ The compounds displayed variable interonium distance, which is believed to range from 11 to 17 Å. ▶ The built in flexibility of these structures resulted in varied degrees of muscle relaxant activity.