thoughts have come to mind, if one were to take such a mesmerizingly close to usefull molecule as phenylethylamine and wanted to say add a halogen to
the para position on the ring, how will this likely affect its biological activity and metabolism? would this perhaps increase half-life? add to
effect profile? and does anyone think that this would be possible without deamination/halogenation/reamination?
forgive me as i sound as if i'm asking to be spoon fed although believe me i have searched and the relevant information does not exist...
this is all merely speculation anyways..
although in my opinion quite an interesting subject. Bolt - 8-4-2011 at 23:25
Most of the para-halogen amphetamines are quite toxic. 4-F amphetamine is by far the least toxic. Would the toxicity of these compounds be extended to
the desmethyl versions? I don't know, but the possibility is probable. Nicodem - 9-4-2011 at 00:04
forgive me as i sound as if i'm asking to be spoon fed although believe me i have searched and the relevant information does not exist...
You searched and found that relevant information does not exist? Either you are a good liar or your literature searching abilities suck. In both
cases, you should know that referenceless threads should be opened in the Beginnings section. If you start from no reference, you start from the
beginning, kind of obvious.oxidativeamination - 9-4-2011 at 00:16
^my apologies nicodem, perhaps my literature searching abilities do indeed suck.. didn't realise that referenceless posts were resricted to
beginnings. been reading the forum for some time though never noted such a case.
i'll do as any dog put in its place and have a better look then shall i. Nicodem - 9-4-2011 at 00:34
perhaps my literature searching abilities do indeed suck..
Indeed they do.
ortho- and para-chlorination: Org. Biomol. Chem., 2006, 4, 2716-2723. DOI:10.1039/B605010G
As for the bromination and iodination, protecting group chemistry needs to be applied, e.g. for iodination: Biochemistry, 2009, 48 (4), pp
688–698. DOI: 10.1021/bi8019977 (the reasons for N-protection have been already discussed on this forum, so improve your searching skills)
Bonus reference about nitration: Journal of the American Chemical Society, 1953, 75, 2069-2072.oxidativeamination - 10-4-2011 at 21:16
thankyou for the references nicodem much appreciated. would you agree with bolt about the toxicity of the para-halogenenated PEA's?
my only real argument for saying they wouldn't be nuerotoxic is that the 2,5-dimethoxy para halogenated PEA's dont seem to be excessively nuerotoxic..
at least nothing like PMA.
can you see anything wrong with this rationalization? or would the 2,5 methoxy groups have some effect of taming the molecules nuerotoxicity??? that
question seems absurd considering that these methoxy's should make it more toxic no?Sedit - 10-4-2011 at 21:46
The first thing that comes to mind is the bulk added buy the 2-5 substitutes will cause it to not interact with the same proteins it might have
otherwise.
""that question seems absurd considering that these methoxy's should make it more toxic no?""
No.. matter of fact I would be more convinced they are whats inhibiting the toxic effects.jon - 11-4-2011 at 16:39
yeah the electron shells of the halogens direct the methoxy groups to perpendicular angles (to the halogen) that's why those 4 sub dimethoxys show a
distinct change in pharmacology. oxidativeamination - 11-4-2011 at 21:48
i've also read in another forum, that N-aceytlation of PEA could be achieved by simply titrating the freebase to the acetate salt followed by
distillation of the salt.
i thought that to achieve N-acetylation of primary amines one would have to reflux them with glacial acetic acid and acetaldehyde.
people on this forum were speculating that the addition of the N-acetyl group would increase resistance to MAO-B/A on first pass. anyone think this
actually contains some validity?
i do suppose that after acetylation it is no longer a mono-amine.
