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Correlations between phototoxicity of some 7-chloro-I,4-benzodiazepines and their (photo)chemical properties

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Abstract

In relation to the phototoxicity of 7-chloro-1,4-benzodiazepine-N-oxides the photostability of some of theseN-oxides and the thermostability of their photoproducts, the oxaziridines, were studied. Rather than a consequence of a direct phototoxic effect by theN-oxides the ultimate toxic effect in the test systemSalmonella typhimurium appeared to be caused by products formed during and after the irradiation. For chlordiazepoxide (Cdz) and its main metabolites in man desmethylchlordiazepoxide (Des) and demoxepam (Dem) the formation of an oxaziridine is indeed a crucial factor for the onset of the toxic effect. However,Dem oxaziridine (Dem Ox.) being very thermolabile in protic medium forms non-toxic conjugates with the solvent,Cdz Ox. andDes Ox. are thermally converted into theirN-oxide, althoughDes Ox. partly decomposes into 6-chloro-4-phenylquinazoline-2-carboxaldehyde as well. This compound proved to be an important factor in the toxic action ofDes after irradiation.

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Authors and Affiliations

  1. Department of Pharmacochemistry, Subfaculty of Pharmacy, State University of Leiden, Gorlaeus Laboratories, P.O. Box 9502, 2300, RA Leiden, The Netherlands

    H. De Vries, G. M. J. Beijersbergen Van Henegouwen & P. J. H. H. Wouters

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  1. H. De Vries
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  2. G. M. J. Beijersbergen Van Henegouwen
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  3. P. J. H. H. Wouters
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In honour of Professor Faber on the occasion of his 25-years' professorate.

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De Vries, H., Beijersbergen Van Henegouwen, G.M.J. & Wouters, P.J.H.H. Correlations between phototoxicity of some 7-chloro-I,4-benzodiazepines and their (photo)chemical properties. Pharmaceutisch Weekblad Scientific Edition 5, 302–307 (1983). https://doi.org/10.1007/BF02074859

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  • DOI: https://doi.org/10.1007/BF02074859

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