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)

Kadi, A.A. and El-Kashef, H.A. and Abdel-Aziz, A.A.M. and Hassan, G. and Tettey, J.N.A. and Grant, M.H. and Lehmann, J. and El-Subbagh, H.I. (2008) 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). ChemInform, 39 (22). ISSN 1522-2667

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Official URL: https://doi.org/10.1002/chin.200822174

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.

Creators(s):	Kadi, A.A., El-Kashef, H.A., Abdel-Aziz, A.A.M., Hassan, G., Tettey, J.N.A., Grant, M.H. ORCID: https://orcid.org/0000-0002-7712-404X, Lehmann, J. and El-Subbagh, H.I.;
Item type:	Article
ID code:	18402
Notes:	Full version of this article published in: Archiv der Pharmazie (2008), 341 (2), pp81-89. PMID: 18214840 (This is a variant record)
Keywords:	multi-membered n-heterocycles, ring closure reactions, pharmacology, medicinal chemistry, vaccines, serums, Bioengineering, Engineering (General). Civil engineering (General), Physical and Theoretical Chemistry, Library and Information Sciences, Computer Science Applications, Computer Graphics and Computer-Aided Design
Subjects:	Technology > Engineering (General). Civil engineering (General) > Bioengineering Technology > Engineering (General). Civil engineering (General)
Department:	Faculty of Engineering > Bioengineering Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user:	Ms Ashley Urie
Date deposited:	26 Mar 2010 15:26
Last modified:	20 Jan 2021 18:31
Related URLs:	Related item Strathprints record
URI:	https://strathprints.strath.ac.uk/id/eprint/18402
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