Which enzyme converts adrafinil to modafinil

[seep]

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Pictorially:

The former is a prodrug of the latter (which is the antinarcoleptic Provigil). The former is hepatotoxic but the latter ain't. So obviously the conversion from hydroxamic acid to acetamide produces a hepatoxic byproduct. What's going on here?

 

[RogueUnicorn]

this is an mcat question and not orgo homework? you can probably bump off the nh-oh group by adding an nh3 to the carbonyl..

 

[seep]

It's not homework.

My question is how adrafinil is converted to modafinil in a liver, not a lab (though thanks!).

I haven't taken biochem yet; hopefully the answer is obvious someone who has. I can't find any info on pubmed about this, nor anywhere else for that matter.

My hunch as to method of hepatotoxicity is that peroxide radical is generated in the conversion from prodrug to active metabolite. Is this reasonable?

 

[GST]

Try looking up phase I metabolism. Or naphthylamine. It has a similar step in its metabolism in the liver.

 

[seep]

Try looking up phase I metabolism. Or naphthylamine. It has a similar step in its metabolism in the liver.

Naphthylamine isn't n-hydroxy:

But hmm...

There's methylenedioxyhydroxyamphetamine,

which is obviously bioavailable in some way, seeing as it's Schedule I. Would this then be a prodrug for MDA?

(sorry, this is the only other n-hydroxylated bioactive compound that comes to mind)

 

[GST]

Naphthylamine isn't n-hydroxy:

True... but one of its metabolites is.

 

[seep]

^That. Is. Scary. As. Hell.

My confusion remains though, as the naphthylamine is oxidated. In contrast, my bioactivation reaction involves a reduction.

When I get done with my tests this week, I'll do a Chemspider substructure search for the hydroxamic moiety to see if I hit upon a substance with well-known pharmacokinetics.

^Scary that thing bonding to DNA like that.

 

[boaz]

This is totally beyond the scope of the MCAT. You might need to know this for more advanced courses but definitely not the MCAT!

 

[seep]

^I like your avatar.

 

[boaz]

^I like your avatar.

Thanks. 🙂 It is real and has been synthesized. I got it from a cool research paper about anthropomorphic compounds.