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- Claesson, Alf, et al.
(författare)
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On Mechanisms of Reactive Metabolite Formation from Drugs
- 2013
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Ingår i: Mini-Reviews in medical chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575 .- 1875-5607. ; 13:5, s. 720-729
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Tidskriftsartikel (refereegranskat)abstract
- Idiosyncratic adverse drug reactions (IADRs) cause a broad range of clinically severe conditions of which drug induced liver injury (DILI) in particular is one of the most frequent causes of safety-related drug withdrawals. The underlying cause is almost invariably formation of reactive metabolites (RM) which by attacking macromolecules induce organ injuries. Attempts are being made in the pharmaceutical industry to lower the risk of selecting unfit compounds as clinical candidates. Approaches vary but do not seem to be overly successful at the initial design/synthesis stage. We review here the most frequent categories of mechanisms for RM formation and propose that many cases of RMs encountered within early ADME screening can be foreseen by applying chemical and metabolic knowledge. We also mention a web tool, SpotRM, which can be used for efficient look-up and learning about drugs that have recognized IADRs likely caused by RM formation.
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| 3. |
- Stroem, Peter, et al.
(författare)
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Tritium labeling of a class of spirooxazaindolamines possessing analgesic properties.
- 2004
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Ingår i: Synth. Appl. Isot. Labelled Compd., Proc. Int. Symp., 8th. ; , s. 285-288
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Konferensbidrag (refereegranskat)abstract
- In order to study the mol. action of a class of spirooxazaindolamines with promising analgesic activity, tritiated material was prepd. Efficient synthesis of 3H-labeled material allowed essential information on the mol. mechanism for this class of compds. to be obtained. Different approaches for the introduction of the 3H-label on the spirooxazaindole skeleton via 3H-methyliodide were evaluated involving lithium-mediated coupling, zinc-mediated coupling and Stille coupling. Tritiation using 3H2 (g) with a Pd-catalyst was also tested. [on SciFinder(R)]
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