Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: mana on July 08, 2019, 01:18:14 AM
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Hi all
I have read in a book ( drug design) that body can convert two enantiomers to each other for example as you know Thalidomide has 2 enantiomers one is teratogenic and the other is a drug, the book says the body can convert the drug to teratogenic enantiomer ???
do you know any other simillar example?
and how it happens?
thanks in advance for your help
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There is Citalopram and Escitalopram (S enantiomer) which are two different drugs, as I read in ncbi once that escitalopram (in my country it's called cipralex or esto) is more potent.
There are many other examples, but not the same case as your drug
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R(-)- into S(+)-ibuprofen
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thanks, so how it happens? have you ever heard anything about that?
and why enantiomeric drugs are not banned? because of dangerous enantiomeric conversion in some cases such as thaliodimide?
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thanks, so how it happens? have you ever heard anything about that?
and why enantiomeric drugs are not banned? because of dangerous enantiomeric conversion in some cases such as thaliodimide?
but not all enantiomers of drugs are bad, they ave to test enantiomers for toxicity these days.
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There are at least two examples of both enantiomers being drugs, although they treat different things IIRC. Darvon and Novrad come to mind.
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How many drugs can the body convert? Are these rather exceptions?
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It depends on the specific structure. Thalidomide racemize because it has quite acidic proton at the chiral center. I can see some chiral secondary alcohol easily racemize via oxidation-reduction sequence but I think those reactions are tested during drug development and if the racemization is occuring, it might stop the drug being developed further or at least forces some structure modifications to stop the racemization. This is, for example, one reason why axially chiral drugs are very rare, because racemization is very easy in those compounds
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Enantiomerically pure (S)-thalidomide enantiomer is teratogenic, while the (R)-enantiomer is not. It seems that yes there is some evidence that the enantiomers of thalidomide interconvert in vivo but teratogenic effects have not observed in animal experiments that use pure (R)-thalidomide.
One theory is that thalidomide enantiomers epimerizes in vivo, followed by precipitation of racemic thalidomide in (R/S)-heterodimeric form. Thus the small amounts of the tetrogenic (S)-thalidomide produced by in vivo racemisation of (R)-thalidomide may be precipitated out as the (R/S) dimer before they can cause birth defects. On the other hand, the 50:50 recemic mixture has enough biologically available (S)-thalidomide to produce birth defects.
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Any
chiral stereogenic center that planarizes or exchanges is liable to racemize.
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Many potential racemization or epimerization reactions are slow in the absence of an appropriate enzyme. For example bacteria have alanine racemase, the existence of which can be explained on the basis of the need for D-alanine as a component of peptidoglycan. To the best of my knowledge mammals lack this enzyme.