• N&PD Moderators: Skorpio | someguyontheinternet

I Like to Draw Pictures of Random Molecules

Status
Not open for further replies.
You get a resonance stabilized cation that could alkylate DNA. I'm not sure to what degree this happens, though, as fluorine is a terrible leaving group.

Uh oh. Ok, I'll keep my fluorines to the ring.

How about some aMT analogues?

20qxhki.png


From left to right, top down: 6-fluoro-aMT, 7-fluoro-aMT, 6-methyl-aMT, 7-methyl-aMT, and my personal favorite, bk-aMT
 
Not sure how stable that ketone will be, cathinones with a primary amine group quickly degrade to the beta-alcohols, have a feeling that one would behave similarly. Those fluorinated aMT's were the kind of thing that Gordon Skinner and Leonard Pickard were developing, 6-fluoro-aMT is described here as being "a beast".
 
Is there anything suggesting anything about how ring halogenation (or even small alkyl substitutions) affects tryptamines; do we have any bases to speculate about SAR?

ebola
 
Not sure how stable that ketone will be, cathinones with a primary amine group quickly degrade to the beta-alcohols, have a feeling that one would behave similarly. Those fluorinated aMT's were the kind of thing that Gordon Skinner and Leonard Pickard were developing, 6-fluoro-aMT is described here as being "a beast".

Cool shit! I was trying to preserve the entactogen action though with these substitutions, note that they aren't jutting off at awkward angles so it can fit through the transporter easily :P
Yes, the beta-keto will likely not be too stable, but cathinone manages to last for long enough for someone to extract/synthesize it and ingest it xD

Is there anything suggesting anything about how ring halogenation (or even small alkyl substitutions) affects tryptamines; do we have any bases to speculate about SAR?

ebola

The other ring-halogenated aMTs (from what wikipedia says) are more psychedelic, and 5-fluoro is an MAOI.
 
cathinone manages to last for long enough for someone to extract/synthesize it and ingest it xD
Does this actually happen? Khat has a shelf life of a few days, do people really use synthetic cathinone? It seems like a lot of hassle for a drug that can't be all that great.
Is there anything suggesting anything about how ring halogenation (or even small alkyl substitutions) affects tryptamines; do we have any bases to speculate about SAR?
lmgtfy ;)
A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin receptor subtypes. The target compounds were evaluated using in vivo behavioral assays for hallucinogen-like and 5-HT1A agonist activity and in vitro radioligand competition assays for their affinity at 5-HT2A, 5-HT2C, and 5-HT1A receptor sites. Functional activity at the 5-HT2A receptor was determined for all compounds. In addition, for some compounds functional activity was determined at the 5-HT1A receptor. Hallucinogen-like activity, evaluated in the two-lever drug discrimination paradigm using LSD-trained rats, was attenuated or abolished for all of the fluorinated analogues. One of the tryptamines, 4-fluoro-5-methoxy-DMT (6), displayed high 5-HT1A agonist activity, with potency greater than that of the 5-HT1A agonist 8-OH-DPAT. The ED50 of 6 in the two-lever drug discrimination paradigm using rats trained to discriminate the 5-HT1A agonist LY293284 was 0.17 μmol/kg, and the Ki at [3H]8-OH-DPAT-labeled 5-HT1A receptors was 0.23 nM. The results indicate that fluorination of hallucinogenic tryptamines generally has little effect on 5-HT2A/2C receptor affinity or intrinsic activity. Affinity at the 5-HT1A receptor was reduced, however, in all but one example, and all of the compounds tested were full agonists but with reduced functional potency at this serotonin receptor subtype. The one notable exception was 4-fluoro-5-methoxy-DMT (6), which had markedly enhanced 5-HT1A receptor affinity and functional potency. Although it is generally considered that hallucinogenic activity results from 5-HT2A receptor activation, the present results suggest a possible role for involvement of the 5-HT1A receptor with tryptamines.
http://pubs.acs.org/doi/abs/10.1021/jm000339w
Looks like you could be on to something with that 6-fluoro-aMT, if that fluoro group knocks out any psychedelic activity but doesn't affect monoamine release then it seems like an analogy could be drawn with N-methylation of MDA, you might be left with a very nice entactogen.
 
I was under the impression that hagitat was the name under which mephedrone (or some blend of substituted cathinones or somesuch) was sold in Israel, rather than cathinone itself. The media reports are rather confused (unsurprisingly), but I don't think that those capsules contained cathinone itself, especially given that it's controlled under the Convention on Psychotropic Substances.
 
6-fluoro-AMT is reportedly active and has been rarely sold as an RC, though I've never seen a trip report. 7-methyl-AMT is a known compound but I'm not aware of anyone trying it.
 
I was under the impression that hagitat was the name under which mephedrone (or some blend of substituted cathinones or somesuch) was sold in Israel, rather than cathinone itself. The media reports are rather confused (unsurprisingly), but I don't think that those capsules contained cathinone itself, especially given that it's controlled under the Convention on Psychotropic Substances.

Oh well you seem to know more about this than me. But in any case, I'm pretty sure that non-methyl cathinones can be synthesized or extracted and used before they degrade too much. There are articles in which methylenedioxycathinone is studied, as well as syntheses/extractions described for cathinone itself.

Also, would N-methylation abolish the releasing activity of aMT?
 
I was under the impression that hagitat was the name under which mephedrone (or some blend of substituted cathinones or somesuch) was sold in Israel, rather than cathinone itself. The media reports are rather confused (unsurprisingly), but I don't think that those capsules contained cathinone itself, especially given that it's controlled under the Convention on Psychotropic Substances.

The Designer Drugs episode of "Drugs Inc" led me to believe hagitat was originally cathinone, then that got banned, and there were several different tweaks made before they landed on mephedrone? Whether they are right or wrong I have no idea!
 
I was under the impression that hagitat was the name under which mephedrone (or some blend of substituted cathinones or somesuch) was sold in Israel, rather than cathinone itself. The media reports are rather confused (unsurprisingly), but I don't think that those capsules contained cathinone itself, especially given that it's controlled under the Convention on Psychotropic Substances.
Oh, well... Isolating cathinone is a bitch due to the dimerisation issue, but the original hagigat (not hagitat btw.) was in fact cathinone HCl. Shortly after, there was rakefet, which was N,N-dimethylcathinone. I know because I was somehow (and kinda unknowingly) involved in the hagigat/rakefet business.

Then came the 2006 ban, followed by the (somehow logical) appearance of mephedrone. By the time meph was banned in Israel in 2008, it was hitting the global RC scene big time. These days, anything sold as hagigat in Israel could very well be meph or one of the fluoromethcathinones (or pretty much anything else; I don't really know because I've lost track).
 
@SerotonergicHaze, I think it's pretty cool. "Theophyllosine triphosphate"? :)

I wonder if it would be active in any way? I guess it would be pretty much inactive if taken orally, judging from how fast oral ATP is chopped to pieces by various gastrointestinal enzymes. I don't think theophylline or caffeine would be formed as metabolites, but perhaps 7-hydroxytheophylline (don't know whether that one is active).

With its similarity to ATP/GTP, I bet it would have some kind of activity if administered by the IV route. IV ATP is active and does have some clinical applications, e.g. in pain management. But this beast could be anything from a competitive adenosine receptor antagonist to a really nasty enzyme inhibitor. Fortunately, it's entirely hypothetical anyway.
 
Was playing in chemsketch
33ortbb.png

Above:
Based on my vague memory of what SSRIs are meant to look like. I could postulate arbitrarily would be most likely a 5-HT and NE reuptake inhibitor, possibly with some sigma agonistic activity

Below: Speaks for it self really
10eikcl.png
 
Status
Not open for further replies.
Top