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.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Kadi AA,El-Kashef HA,Abdel-Aziz AA,Hassan GS,Tettey J,Grant MH,Lehmann J,El-Subbagh HIdoi
10.1002/ardp.200700132subject
Has Abstractpub_date
2008-02-01 00:00:00pages
81-9issue
2eissn
0365-6233issn
1521-4184journal_volume
341pub_type
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