Metabolism of 2-Amino-1,2-dihydronapthalene (2-ADN)

Hello ADDers,

Through my looking around at various amphetamine analogs I came across this:



It's pharmacologically active and roughly 1/4 potency of dextroamphetmine. But it's not the activity that I'm interested in, it's the metabolism. I would assume that 2-napthylamine is also pharmacologically active, but it's extreme toxicity/carcinogenity would obviously rule out any use for it.

So my question is, is this likely to metabolise in a much less toxic way, and if so what to? Does the partial saturation of a ring avoid epoxidation?

I wouldn't touch that with a barge pole. From what I remember, tetralins are wont to cause seizures and other freaky stimulant side effects, but not euphoria.

Well, but that's not a tetralin. A tetralin would have the other double bond on that ring saturated too...

I wouldn't ever ingest something like that either though, owing to it's structural similarity to tetralins and napthalene-derivatives.

We have a universe of phenmetrazine and aminorex derivitives, many of which are surprisingly easy to synth... and we're instead replacing phenyl groups with napthyl (or in this case dihydronapthyl, or tetralinyl (?) in several other cases) and acting surprised when they turn out to be nasty shit.

It looks unsafe to me (too similar to 2-aminonaphthalene, a potent cancer-inducer)
http://en.wikipedia.org/wiki/2-Naphthylamine

I'm not particularly interested in ingesting this substance either, I was just curious as to how it would metabolise. If it presents a route of metabolism that is much more preferable to epoxidation, then perhaps some of those other chemicals with napthyl groups can be replaced with partially saturated napthyl groups. For example, most cannabinoid receptor ligands have a need for a big bunch of carbon in part of the structure, and those that contain napthyl groups may undergo pyrolysis and have napthalene as a product of decomposition - by using a dihydronapthyl group instead, you could avoid this (provided it actually metabolises better, otherwise there's not much point).

If i want legal stimulants to actually ingest myself, I know there are already a multitude of them out there with much more data published.

For those of you worried about napthalene and its derivatives, you need to remember it's not the napthalene itself that causes the damage, it's the epoxide metabolite that wreaks havoc. If you don't get the epoxide, it's not an issue.

This is not a tetralin - the partially saturated ring of 1,2 dihydronapthalene is more rigid than for tetralins - the floppy nature of tetralins' saturated rings tends to make them less specific as far as pharmacological action is concerned.

Someone posted here a long time ago saying the aminotetralin compound had mild effects in the 100-200mg range and then seizures and unconsciousness slightly above that. I had wondered if this was the effect of some sort of metabolite for a while as the rats seem to do okay, but I have no idea really.

I think that it's sort of a race between two metabolic pathways, one producing the usual epoxides and phenyl diols and the other how primary aromatic amines are metabolized which is R-NH2 → R-NHOH → R-N=O → R-NO2
Apparently in animal tests there has been association shown with carcinogenesis with the PAAs.

So neither are good and it's probably best avoided.

Oh wait no it's not a naphthyl, so the path to the nitro is a different one. Not sure how much that matters. Isn't it possible that when the R=NH is formed there is a tautomerization that makes epoxidation more likely to happen?

does it not undergo deamination to the hydroxyl, followed by oxidation and rearrangement to 2-hydroxynaphthylene (no epoxide intermediate)? At a guess though, I reckon most would be excreted unmetabolized as the amino group makes it easy for the kidneys to remove