Drugs, Racemic Mixtures, Data Curation and Tautomers

09 Feb

Yes, that’s quite a title for a blog post. But it covers the nature of exchanges that Egon Willighagen and I have been having recently (that among others as we are co-authoring a book chapter on Computational Toxicology also). Egon asked a question on the Blue Obelisk Discussion group about tautomers and I answered it on this blog. Egon has posted a follow up blog post here. His most recent post makes a series of valid comments…all good and well worth discussing.

Egon then asked about one of the compounds on ChemSpider here saying

“Anyway. Tautomerism was a curation issue in the first(!!!) entry I was curating. The sixth had the more well-known problem, I think. I may be blind, but I would say this drug has a stereocenter:

But none of the databases I checked so far (including ChemSpider) defines the stereochemistry! I thought we settled that some decades ago? Stereochemistry of drugs matter. What is going on here?”.

The drug shown is Aminoglutethimide. It’s on Wikipedia here without specific stereochemistry. But as we know Wikipedia does have errors (see slide 47/126 here). So what gives? It’s on KEGG in the same way. Also on ChEMBL here. But it IS on ChemSpider as both stereoforms….R and S. I would suggest that the drug is likely a racemic mixture of the stereoforms and as represented on all of the databases it’s probably okay to not draw the stereobonds as there is only one stereocenter to worry about. Checking Dailymed supports this in this record. A search on “Aminoglutethimide” gives 36000 hits on Google…I did not wade through them! I think the drug is therefore supplied as a racemate, can be separated (see top google hits) but is okay on ChemSpider as is.


2 Responses to Drugs, Racemic Mixtures, Data Curation and Tautomers

  1. Egon Willighagen

    February 10, 2011 at 12:07 am

    Yes, I was told by @chembl too that the drug is administered as a racemate. I guess I had too much stress on DES in my education to not realize that we still have drug where the stereo doesn’t matter 🙂 A bit embarrassing to not have realized this when I wrote up that post… but it doesn’t entirely solve my problem either: how should this be represented in QSAR modeling… one properties, two structures… that got me one the wrong foot, I guess.

  2. Egon Willighagen

    February 10, 2011 at 12:10 am

    Oh, and it made me also realize something else… compound databases are basically unsuitable to represent such drugs! Or, put differently, compound databases (when they contain drugs like this) are not pure compound databases, but compound/mixture databases… but I have the first database to encounter to have a red label saying “Watch it! This entry is a racemic mixture! Not a unknown stereochemistry!”


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