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a potentially new compound

P

pyridineman

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Joined
Dec 2, 2021
Messages
3
Hey i came up with 2 new molecules and wondering what would be the potential effects of it

the metabolism pathway is worrying, i have a feeling this might be a longer lasting molecule with harmful metabolites or intermediates


 
If you take off the aromatic -CH3, they will work though.
 
pyridineman said:
what if i hydrogenate it? so replace the regular N with NH, would result in a more stable compound
any ideas into what it might metabolize?
Click to expand...
If hydrogenated it won't be planar, so will at best be something like propylhexidrine.

Maybe if the pyridine ring was rotated a bit so the nitrogen is untouched.

I still worry that the lone pair of the nitrogen will do something wonky to its binding profile, also a methyl ortho to the nitrogen will confer aldehyde oxidase affinity which could be a good thing (shorter duration) but will introduce pretty novel metabolites (possibly bad).

Honestly I'd like to see a pharmacological workup of the unsubstituted pryidine (let's say with the nitrogen in ortho, meta and para to the ethylamino before getting into ring substitutions.

Also remember that 4 methyl amphetamine is one of those maoi + serotonin releasers that have a steep enough dose response to accrue a pretty high body count.
 
Skorpio said:
If hydrogenated it won't be planar, so will at best be something like propylhexidrine.

Maybe if the pyridine ring was rotated a bit so the nitrogen is untouched.

I still worry that the lone pair of the nitrogen will do something wonky to its binding profile, also a methyl ortho to the nitrogen will confer aldehyde oxidase affinity which could be a good thing (shorter duration) but will introduce pretty novel metabolites (possibly bad).

Honestly I'd like to see a pharmacological workup of the unsubstituted pryidine (let's say with the nitrogen in ortho, meta and para to the ethylamino before getting into ring substitutions.

Also remember that 4 methyl amphetamine is one of those maoi + serotonin releasers that have a steep enough dose response to accrue a pretty high body count.
Click to expand...
im not really going wild with ring substitutions here by hydrogenating it, its only to make the compound stable and resistant to forming into a potentially harmful metabolite
from there doing experiments with ortho/para/meta rotations should be fun

thanks for the input, deeply insightful
 
pyridineman said:
im not really going wild with ring substitutions here by hydrogenating it, its only to make the compound stable and resistant to forming into a potentially harmful metabolite
from there doing experiments with ortho/para/meta rotations should be fun

thanks for the input, deeply insightful
Click to expand...
Hydrogenating it makes it non-planar though. Pyridine and benzene rings are totally flat but cyclohexanes and piperidine rings exist in a puckered conformation. This not only won't fit into the same pockets as a planar molecule, but lacks a conjugated electron system that is important for pi stacking interactions with aromatic amino acids.

 
As @Rectify said, N-substituted pyridines are positively charged (and it doesn't change with pH). If you took away the methyl group you would end up with a regular substituted pyridine ring, it has a pKa of around 5.2, so the N-H form would be pretty minoritary at physiological pH. The issue with pyridines is that the nitrogen atom is decently nucleophilic, meaning it has a tendency to react with electrophiles (which is usually a bad thing). Another thing to consider is that the pyridine ring is electron deficient (π-deficient) so it doesn't work very well if you're looking for π-stacking interactions with a given receptor.
 
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I took 3-aza-methamphetamine.hcl once.
It lasted a while but not as buzzy as ICE.
 
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