phenyl eth-en-yl amine [PEeA] - SAR?

[gladiolus]

with PEA, modifications to the alpha position prevent reduction [eg amphetamine]: to a lesser extent so does beta substitution. Some pharmaceuticals bind the two, [eg tranylcypromine]. But has anyone ever thought of investigating a double-bond modification to the PEA over the alpha-beta positions to produce phenylethenylamine?
This molecule also has the strange property that if it is bent over onto the phenyl, it produces the indole molecule.

These 2 observations give me reason to suspect high pharmocological activity of PEeA, either DRA and NRA actions, or MAOI actions, quite possibly both. Yet sustained internet investigation produces not results of investigation of this compound.

What possible alterations of physiological effects could one expect from introducing this double bond? A longer-lasting PEA compound? Or something completely different?

 

[atara]

It would quickly tautomerize to the imine, which hydrolyses to phenylacetaldehyde.

 

[Hammilton]

I was just gonna write the same thing. but yeah.

what about alpha methyl derivatives with that double bond?

 

[atara]

I was just gonna write the same thing. but yeah.

what about alpha methyl derivatives with that double bond?

Uh? In order to keep it from tautomerizing, you'd have to go as far as alpha-vinyl, I think. I think you might see irreversible MAO-inhibitor activity, owing to the reactivity of the alkene. Similar alkyne-substituted phenethylamines are used as irreversible MAOIs.

 

[Hammilton]

are you talking about (E)-1-phenylprop-1-en-2-amine or alpha-methylene-PEA? the former is my question. I ask because I don't understand why you go to an alpha-vinyl substitution (why not a plain longer alkyl?)

 

[<pyridinyl_30>]

The same thing would happen to alpha-methylene-pea upon contact with water.

 

[atara]

The same thing would happen to alpha-methylene-pea upon contact with water.

Yeah. Alpha-vinyl is the shortest unsaturated phenethylamine derivative that would be stable in water, unless you count phenethyloxime.

 

[dread]

Beta-methylene-phenethylamine is shorter.

 

[Hammilton]

So (E)-1-phenylprop-1-en-2-amine will be as well?

 

[atara]

Beta-methylene-phenethylamine is shorter.

Man I hate it when you're right.

 

[wungchow]

i suppose you could have something like this?

 

[Saucy]

^wouldn't that still undergo hydrolysis?

 

[dread]

i suppose you could have something like this?

Sure, if you want to have something that quite likely hydrolyzes into aniline?

 

[atara]

Sure, if you want to have something that quite likely hydrolyzes into aniline?

DBU doesn't hydrolyse that easily; the amidines are more stable than the imines, I think.

The problem is that there's no reason at all to believe the damn thing would cross the BBB, since it's charged at biological pH, much less be active.

 

[dread]

DBU doesn't hydrolyse that easily; the amidines are more stable than the imines, I think.

The problem is that there's no reason at all to believe the damn thing would cross the BBB, since it's charged at biological pH, much less be active.

Well, aniline could still be a metabolite... I wouldn't put that stuff in my body. No way.

 

[Limpet_Chicken]

How about the equivalent with an ethynyl triple bond?

 

[dread]

^ I can't imagine that kind of chemical to be very stable... alkynes tend to be reactive, so I'm told.

 

[Limpet_Chicken]

Figured it would be, asked anyway, one does not, one does not gain knowledge.

 

[mimac]

i suppose you could have something like this?

I don't think this would cross the bbb

 

[dread]

Figured it would be, asked anyway, one does not, one does not gain knowledge.

That's a smart attitude for one.