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)

A.A. Kadi, H.A. El-Kashef, A.A.M. Abdel-Aziz, G. Hassan, J.N.A. Tettey, M.H. Grant, J. Lehmann, H.I. El-Subbagh

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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.
LanguageEnglish
JournalChemInform
Volume39
Issue number22
DOIs
Publication statusPublished - 27 May 2008

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Hypnotics and Sedatives
carboxylates
rats
anesthesia
Rats
liver
Liver
synthesis
profiles
Sodium
sodium
pharmaceutical
Thiopental
anesthetics
tolerance
Anesthetics
medication
urine
animal
Liquid chromatography

Keywords

  • multi-membered n-heterocycles
  • ring closure reactions
  • pharmacology
  • medicinal chemistry
  • vaccines
  • serums

Cite this

Kadi, A. A., El-Kashef, H. A., Abdel-Aziz, A. A. M., Hassan, G., Tettey, J. N. A., Grant, M. H., ... 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). https://doi.org/10.1002/chin.200822174
Kadi, A.A. ; El-Kashef, H.A. ; Abdel-Aziz, A.A.M. ; Hassan, G. ; Tettey, J.N.A. ; Grant, M.H. ; Lehmann, J. ; El-Subbagh, H.I. / 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). In: ChemInform. 2008 ; Vol. 39, No. 22.
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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.",
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author = "A.A. Kadi and H.A. El-Kashef and A.A.M. Abdel-Aziz and G. Hassan and J.N.A. Tettey and M.H. Grant and J. Lehmann and H.I. El-Subbagh",
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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.; El-Kashef, H.A.; Abdel-Aziz, A.A.M.; Hassan, G.; Tettey, J.N.A.; Grant, M.H.; Lehmann, J.; El-Subbagh, H.I.

In: ChemInform, Vol. 39, No. 22, 27.05.2008.

Research output: Contribution to journalArticle

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T1 - 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)

AU - Kadi, A.A.

AU - El-Kashef, H.A.

AU - Abdel-Aziz, A.A.M.

AU - Hassan, G.

AU - Tettey, J.N.A.

AU - Grant, M.H.

AU - Lehmann, J.

AU - El-Subbagh, H.I.

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Y1 - 2008/5/27

N2 - 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.

AB - 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.

KW - multi-membered n-heterocycles

KW - ring closure reactions

KW - pharmacology

KW - medicinal chemistry

KW - vaccines

KW - serums

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JO - ChemInform

T2 - ChemInform

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SN - 0931-7597

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