The open-ring analogs of benzodizepine sleep inducers

Abstract

Gastrointestinal absorption rate of benzodiazepines are relatively fast despite their water-insoluble characteristics in vitro. One of the reasons is their reversible reaction in acidic media simulated to stomach contents at 37 °C to produce the open-ring derivatives of the corresponding benzodiazepines, which are soluble in acidic environment because of the primary amine substituents formed. 450191-S, one of the open-ring compounds of benzodiazepines, is being developed as a water-soluble prodrug of benzodiazepine. Larger AUC of the active metabolite was reported after oral administration of 450191-S than corresponding benzodiazepine because of the avoidance of the hapatic first-pass extraction.