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N&PD Moderators: Skorpio | thegreenhand
Cocaine Replacement
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Nagelfar
Bluelight Crew
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- Nov 23, 2007
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clubcard, I was thinking for ease of synthesis, the cocaine "piperidine homologues" (benzoyloxy intact) have bad affinity it seems; but according to Singh's cocaine paper (jump to page #44) the phenyltropane piperidine homologues are just as good as any phenyltropane itself. Why not go that route then? Surely the synthesis would be much easier:
Amazing how close it is to phenmetrazine, it seems the atomic length being one bond longer or shorter from the phenyl to the nitrogen makes the difference between a dopamine re-uptake inhibitor (inverse agonist?) and dopamine releasing agent (DAT substrate)
So would a reverse methyl-nitrogen methamphetamine make a good "inverse agonist" (or for those of a more conventional leaning, "typical/open-to-out-binding" re-uptake pump ligand?) *instead* of a releaser?
...back to the top compound, tethering the nitrogen via Dieckmann cyclization with the tropanes always increased the affinity greatly by constraining the nitrogen's place, perhaps doing similar to that with just the piperidine, and we get that chair conformation again, perhaps more cocainesque with even better affinity:
three bonds through middle & two bonds, respectively. A sole bond makes it very boxy (third image)
^A cyclopentane gives it both the four bond length for a DRI and the three bond length for a DRA, usually DRAs also act as DRIs only in large concentrations; perhaps this'd work similar in smaller concentrations if other pharmacokinetic factors do not inhibit its intended function?
Amazing how close it is to phenmetrazine, it seems the atomic length being one bond longer or shorter from the phenyl to the nitrogen makes the difference between a dopamine re-uptake inhibitor (inverse agonist?) and dopamine releasing agent (DAT substrate)
So would a reverse methyl-nitrogen methamphetamine make a good "inverse agonist" (or for those of a more conventional leaning, "typical/open-to-out-binding" re-uptake pump ligand?) *instead* of a releaser?
...back to the top compound, tethering the nitrogen via Dieckmann cyclization with the tropanes always increased the affinity greatly by constraining the nitrogen's place, perhaps doing similar to that with just the piperidine, and we get that chair conformation again, perhaps more cocainesque with even better affinity:
three bonds through middle & two bonds, respectively. A sole bond makes it very boxy (third image)
^A cyclopentane gives it both the four bond length for a DRI and the three bond length for a DRA, usually DRAs also act as DRIs only in large concentrations; perhaps this'd work similar in smaller concentrations if other pharmacokinetic factors do not inhibit its intended function?
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