Methylphenidate analogue of tryptamine

[Reminisant B]

(1H-Indol-3-yl)-piperidin-2-yl-acetic acid methyl ester

Anyone think this will have serotonin reuptake properties? Possibly the logic is slightly hazy!

But seriosly anyone know if the piperadine ring structure works for tryptamines?

Looking at the chem 2d the Oxygen on the ester looks like its hitting the 4 position.

 

[Reminisant B]

Whilst not the structure I was thinking about apparently there is a potential anti-depressant compound indalpine...

(1H-Indol-3-yl)-piperidin-2-yl-acetic acid methyl ester

Something new every day

 

[Morninggloryseed]

Seems once the amine is 4 or 5 carbons away from the rings (instead of 2) we get into AD territory.

 

[haribo1]

^^^Yep, I've noticed that. If you add halides or pseudohalides to the ring systems you seem to get antipsychotics...

 

[mad_scientist]

I've always thought it's interesting that amphetamine and AMT are both stimulants and both have an aromatic ring attached to an isopropylamine side chain. Makes me wonder if you could substitute other aromatic rings to get active stimulants.

Works with other series of drugs, i.e. PCP --> TCP, thiophene ring instead of phenyl; diazepam --> bromazepam, pyridine ring instead of phenyl. Both of those substitutions retain activity. So i don't see why using other aromatic rings instead of the phenyl ring of amphetamine wouldn't be a possible strategy.

F&B has said before that the thiophene analogue of amphetamine is not an active stimulant, but i don't think the pyridine analogue has ever been tested.

Seeing as the benzothiophene analogue of DMT is an active hallucinogen (S instead of NH in the indole ring) then the benzothiophene analogue of AMT might be an active stimulant.

And seeing as there are many stimulants with an unsubstituted phenyl ring, methylphenidate, methylaminorex, phenmetrazine, fencamfamine for instance, it could be worth looking at analogues of any of those but with different aromatic rings instead.

 

[Morninggloryseed]

Seeing as the benzothiophene analogue of DMT is an active hallucinogen (S instead of NH in the indole ring) then the benzothiophene analogue of AMT might be an active stimulant.

.

I think I have seen this somewhere, nevertheless do you have a citation?

 

[mad_scientist]

Replacement of NH with S in indole ring:

Bosin, T. R.; Campaigne, E. E. Biologically active benzo-
thiophene derivatives. II. Adv. Drug Res. 1977, 11, 191-232.

They do say that it changes the pharmacology slightly but unfortunately i don't have free web access to that article


Replacement with phenyl portion of indole ring with thiophenyl:

Joseph B. Blair, Danuta Marona-Lewicka, Arthi Kanthasamy, Virginia L. Lucaites, David L. Nelson, and David E. Nichols. Thieno[3,2-b]- and Thieno[2,3-b]pyrrole Bioisosteric Analogues of the Hallucinogen and Serotonin Agonist N,N-Dimethyltryptamine. J. Med. Chem. 1999, 42, 1106-1111.


Interestingly one of the refs from that second one says "the thiophene analogue of amphetamine retains complete amphetamine-like activity"

Foye, W. O.; Tovivich, S. Heterocyclic analogues of amphetamine:
Thioureas, dithiocarbamates, and negatively substituted
amides. J. Pharm. Sci. 1979, 68, 591-595.