Synthesis, ultra-short acting hypnotic activity, and metabolic profile of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a] [1,3]diazepin-3-carboxylate (HIE-124)

Archiv der Pharmazie
Adnan KadiHussein El-Subbagh

Abstract

The synthesis and biological evaluation of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 4), as a member of a new generation of ultra-short acting hypnotics is described. HIE-124 4 exhibited potent in-vivo activity with a very rapid onset of action and a shorter duration of action with no acute tolerance or noticeable side effects than thiopental sodium. The rat in-vivo and in-vitro metabolic profile of 4 is also described. Urine was pooled from a number of animals and analyzed using electrospray liquid chromatography mass spectrometry (ESI LC-MS). HIE-124 4 was incubated with rat-liver microsomal and rat-liver hepatocyte preparations then similarly analyzed. The only metabolic product of both in-vitro and in-vivo experiments is the carboxylic acid derivative 5. HIE-124 4 has the potential use not only as a pre-anesthetic medication and as anesthesia inducer but also has the potential to be used with thiopental sodium to maintain anesthesia for longer duration.

References

Mar 1, 1977·Clinical Pharmacokinetics·D D Breimer
Mar 1, 1992·Anesthesiology·S L Shafer, D R Stanski
Jan 1, 1991·Methods in Enzymology·J L Raucy, J M Lasker
Jan 1, 1990·Journal of Pediatric Surgery·J AikenJ P Vacanti
May 13, 1993·The New England Journal of Medicine·R I Shader, D J Greenblatt
Jul 24, 2001·Current Drug Metabolism·B C SallustioR L Nation
May 23, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan E H AlexsonStellan Swedmark
Oct 26, 2002·Chemico-biological Interactions·Saileta PrabhuAlbert P Li
Jan 3, 2006·Biochemical Pharmacology·Matthew K RossPhilip M Potter
Aug 23, 2006·Expert Opinion on Drug Metabolism & Toxicology·Olavi Pelkonen, Hannu Raunio

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Citations

Oct 16, 2013·European Journal of Medicinal Chemistry·Ahmed R AliIhsan A Shehata
Mar 2, 2021·Medicinal Research Reviews·Yohan MalkiNicolas Masurier

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