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. Ei-Kashef, A.A.M. Abdel-Aziz, G.S. Hassan, J.N.A. Tettey, M.H. Grant, J. Lehmann, H.I. EI-Subbagh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 preanesthetic medication and as anesthesia inducer but also has the potential to be used with thiopental sodium to maintain anesthesia for longer duration.
LanguageEnglish
Pages81-89
Number of pages8
JournalArchiv der Pharmazie
Volume341
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Metabolome
Hypnotics and Sedatives
Anesthesia
Electrospray Ionization Mass Spectrometry
Liver
Carboxylic Acids
Liquid Chromatography
8-oxo-5,6,7,8-tetrahydro-thiazolo(3,2-a)(1,3)diazepin-3-carboxylate
Urine

Keywords

  • metabolic profile
  • synthesis
  • thiazolo[3
  • 2-a][1
  • 3]diazepine
  • ultra-short acting hypnotic

Cite this

Kadi, A. A., Ei-Kashef, H. A., Abdel-Aziz, A. A. M., Hassan, G. S., Tettey, J. N. A., Grant, M. H., ... EI-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). Archiv der Pharmazie, 341(2), 81-89. https://doi.org/10.1002/ardp.200700132
Kadi, A.A. ; Ei-Kashef, H.A. ; Abdel-Aziz, A.A.M. ; Hassan, G.S. ; Tettey, J.N.A. ; Grant, M.H. ; Lehmann, J. ; EI-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: Archiv der Pharmazie. 2008 ; Vol. 341, No. 2. pp. 81-89.
@article{fdf668f5d9ee4b589cd40511d45aa88b,
title = "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)",
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 preanesthetic medication and as anesthesia inducer but also has the potential to be used with thiopental sodium to maintain anesthesia for longer duration.",
keywords = "metabolic profile, synthesis, thiazolo[3, 2-a][1, 3]diazepine, ultra-short acting hypnotic",
author = "A.A. Kadi and H.A. Ei-Kashef and A.A.M. Abdel-Aziz and G.S. Hassan and J.N.A. Tettey and M.H. Grant and J. Lehmann and H.I. EI-Subbagh",
note = "Abstract also published in: ChemInform (2008), http://dx.doi.org/10.1002/chin.200822174",
year = "2008",
month = "2",
doi = "10.1002/ardp.200700132",
language = "English",
volume = "341",
pages = "81--89",
journal = "Archiv der Pharmazie",
issn = "0365-6233",
number = "2",

}

Kadi, AA, Ei-Kashef, HA, Abdel-Aziz, AAM, Hassan, GS, Tettey, JNA, Grant, MH, Lehmann, J & EI-Subbagh, HI 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)' Archiv der Pharmazie, vol. 341, no. 2, pp. 81-89. https://doi.org/10.1002/ardp.200700132

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.; Ei-Kashef, H.A.; Abdel-Aziz, A.A.M.; Hassan, G.S.; Tettey, J.N.A.; Grant, M.H.; Lehmann, J.; EI-Subbagh, H.I.

In: Archiv der Pharmazie, Vol. 341, No. 2, 02.2008, p. 81-89.

Research output: Contribution to journalArticle

TY - JOUR

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 - Ei-Kashef, H.A.

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

AU - Hassan, G.S.

AU - Tettey, J.N.A.

AU - Grant, M.H.

AU - Lehmann, J.

AU - EI-Subbagh, H.I.

N1 - Abstract also published in: ChemInform (2008), http://dx.doi.org/10.1002/chin.200822174

PY - 2008/2

Y1 - 2008/2

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 preanesthetic 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 preanesthetic medication and as anesthesia inducer but also has the potential to be used with thiopental sodium to maintain anesthesia for longer duration.

KW - metabolic profile

KW - synthesis

KW - thiazolo[3

KW - 2-a][1

KW - 3]diazepine

KW - ultra-short acting hypnotic

UR - http://dx.doi.org/10.1002/ardp.200700132

U2 - 10.1002/ardp.200700132

DO - 10.1002/ardp.200700132

M3 - Article

VL - 341

SP - 81

EP - 89

JO - Archiv der Pharmazie

T2 - Archiv der Pharmazie

JF - Archiv der Pharmazie

SN - 0365-6233

IS - 2

ER -