Stimulants 3-FPO / 3FPO New Oxadiazol-based PEA

[Soulfake]

I got a G sample of this in the mail and wanted to ask what people think about this and if there are already faster labowls with experiences?

First reports sound a bit too good, something about similar to 3FPM and Amphetamine and derived from 4F-MPH although personally I can't compare both on the same level, 3FPM is very different from all Ephe/Amph/Cath stuff and feels really sedating for me, and after seeing how many possible metabolites this stuff can form, I really don't wonder about cardiovascular side effects that had been observed as well as why the non-halogenated one was used to stop hunger as there seem to be many metabolites with those "body building booster" thingy structures or how they are called, with those octopamine synephrine whatever pseudo-stims that mainly raise blood pressure etc.

Somehow I find those structures a bit scary with those extra nitrogens and older drugs with such configurations like Pemoline were as problematic as my gut feeling tells me, although others like Cyclazodone and Methyl-Cyclazodone seem to be less harmful but I wonder how they can state that without many studies and years of experience, usually it takes 15 years until a drug is really "researched" and further classified according to the severity of side effects and also the worldview of those deciding about it (just look at the sildenfinil situation where it gets more and more OTC in many countries as there simply haven't been any problematic effects been observed in healthy people so there is no reason to forbid adult people to put it into their body, but in Germany the buerorats instantly think "oh no that cannot be allowed people can't use it responsibly people are too dumb" (even though everyone can legally get a online prescription without any further questions etc., and everyone can put holes into his stomach legally with too many headache meds...)

5-((3-fluorophenyl)(piperidin-2-yl)methyl)-3-methyl-1,2,4-oxadiazol
FC=1C=C(C=CC1)C(C1=NC(=NO1)C)C1NCCCC1

SwissTargetPrediction

 

[4DQSAR]

I recall a team researching various methylphenidate derivatives a few years ago so I'm pretty sure it WAS tested. I belive it only ever underwent in vitro testing. So we have no way of knowing what the metabolism will be.

That meta fluoro moiety would have pushed up the synthetic cost so included to provide a specific activity or needed for the compound to demonstrate ANY activity?

If it hasn't undergone human trials - YOU ARE the human trial. The risk, I have always thought is that 99 people could consume something so novel and be fine - only to discover that due to genetic differences, the 100th person does have a negative reaction.

I would have gone for a para methyl or meta methyl first because it appears that a lot of enzymes will oxidize that methyl and produce a fairly reliable metabolic pathway. I mean over an example with no ring-substitution. But who knows? Maybe it was tried, maybe it wasn't.

I just use what I term 'defensive design' stratergy i.e. go for something where you can make a reasonable prediction of metabolism.

Still, interesting stuff.

 

[Esperighanto]

I'm excited to hear more about this, phenidates and relatives (phenylmorpholines, tricyclic compounds like pipradol and desoxypipradol, etc.) are some of my favorite compounds. Has anybody ever explored something like 2,5-dimethoxy-4-halogenated substitutions on the phenyl heterocycle? I suspect that since the same substitutions on phenmetrazine make a weak, though active psychedelic, perhaps something similar could some day arise in the world of phenidates.

 

[4DQSAR]

I, for one, would appreciate some reference for such a novel compound.

The closest I can find is: this:

2-[(4-Fluorophenyl)(3-methyl-1,2,4-oxadiazol-5-yl)methyl]piperidine

2-[(4-Fluorophenyl)(3-methyl-1,2,4-oxadiazol-5-yl)methyl]piperidine | C15H18FN3O | CID 165460837 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

EN300-37293661
2-[(4-fluorophenyl)(3-methyl-1,2,4-oxadiazol-5-yl)methyl]piperidine
CAS 2743442-63-7

The para fluoro positional isomer of the pictured compound. A few ligand suppliers offer it.

Now examples without that para fluoro AREN'T listed as far as I can tell. The meta fluoro isn't listed either. In fact, NO homologues are listed.

So why the meta fluoro? It appears the para fluoro compound was only added in 2022 but the meta fluoro isn't.

I checked Chemspider, Chemical Book, Molecule Finder & Chemsource as well and no further data was found.

EnamineStore

www.enaminestore.com

Above is a link to a ligand supplier who doesn't sell to individuals so I think can be ruled out as a source. I enclose it because it includes the SDS of the positional isomer. I lack the technical skill to provide a link directly to that SDS. I'm hoping a mod can isolate that SDS so potential tasters have at least the best data I can find.

I would suggest someone invest in having GC-MS and NMR analysis carried out to see if it is the meta or if in fact it's the para. I mean, better safe than sorry and knowing for sure what you have is important in staying safe.

BTW that code name beginning with EN suggests that Enamine are the discoverrs of the para fluoro positional isomer.

 

[Esperighanto]

I lack the technical skill to provide a link directly to that SDS. I'm hoping a mod can isolate that SDS so potential tasters have at least the best data I can find.

I actually had a ton of trouble figuring out how to link to it, since it's not a separate download link as much as it's a page on a website. I wouldn't be super shocked if there's an analog being made of the para-fluoro isomer that is the meta-fluoro. It's probably weaker, and I'd be willing to bet that this is an attepmt to get around 4F-MPH bans in places like NL. Just my guess on the matter.

 

[4DQSAR]

@Esperighanto I really appreciate your feedback and I think you may well be right. My issue is that it's unclear to me what metabolic pathway(s) might be involved when the labile ester function is swapped for an aromatic.

I did search Google patents looking for Enamine patents but found nothing.

So I took the step of contacting Enamine asking for reference.

I SUSPECT that if a patent exists, if the compound only turned up in 2022 such a patent would still be in place. But the fact that they don't offer the meta fluro compound OR the unsubstituted parent compound MAY suggest that the para fluoro compound represents a 'small island of activity'. Or, equally possible, it's merely weaker and thus not as useful as a research ligand. Both make some sort of sense.

But I would love to see a GC-MS / NMR instrumental analysis of the product offered. Maybe they have something truly novel, Maybe not.

Only that analysis can confirm. I am not convinced that a simple 'druglikeness' webform in any way confirms utility or, more importtantly, safety. Legal comes a long way after 'safe' in my ethos.

I can't help thinking that there are things like pyrophenidone which is a bioisostere of pyrovalerone - the para methyl both increasing activity and reducing duration. If you simply MUST have crazy potent, JNJ-7925476 is part of a series and the interesting thing is that like the simple PEA-based compounds, various meta and para substituents were also tested so in theory, one can 'tune' the results in a subtle manner. While it has undergone in vivo models using rodents, I would still approach with great care. Sub nM affinity for the three monoamine transports makes for something that may be highly active... but as for human safety? None carried out as best I can tell.

But at least JNJ-7925476 HAS many academic papers and indeed patents thus we know a little biit more than we do with this stuff.

Quite honestly surprised that para ethynyl amphetamine was also offered as a research ligand and I'm honestly surprised that nobody has thought to try the beta ketone derivative. Why that and not the simple amphetamine? Metabolism. It would almost certainly be less potent but don't forget that while methadrone was reasoably non-toxic, p-TAP was mush more dubious. I had call to look at a cluster of deaths in and around Greater Manchester and some genius had figured out that mixing p-TAP with amphetamine estimated MDMA. But p-TAP appears to be an MAOI. Certainly it was misrepresented to consumers.

I hope my explaination is understandable to others.

It's been my experience that people under the influence of psychoactive sometimes make bad decisions. So in a way, you have to 'idiot proof' a design. If something is VERY potent, I don't think powder appropriate. Invest in a press and batch-test. At least that way know what they had and how much they had.

​

 

[4DQSAR]

https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf#50

'The3â-(substituted phenyl)-2â-(3′-substituted 1 2′,4′-oxadiazol-5′-yl)tropanes (31,32a-f, 33; (Figure 9)) were designed becauset the1,2,4-oxadiazole ring is a bioisostereo of the carbomethoxy group and also stable to chemical and enzymatic degradation.'

The closest I can find is examples in which the methyl ester moiety found in cocaine was substituted with the 1,2,4-oxadiazole aromatic (page 938-940).

I note that all of the examples feature a para substituted benzene ring. It may just be a limitation of scope of research or may be important to activity. But that 3-methyl MAY be incorporated to provide a labile moiety for metabolism. But without data, that's just a guess. Equally they may increase activity or indeed do both,

So inching towards finding the data but so little is known, Well, 16+ hours of searching and this is all I have along with a couple of patents that MIGHT cover it but use click-chemistry and Markush structures so I can't be certain.

The 'elephant in the room' is the fact that che compound (whichever one it turns out to be) is chiral. I hope I don't need to remind people that the four enantiomers may have significantly different activity inclusing different metabolic fates. So any research would need to address that issue.

I just can't help thinking that homologues of Levophacetoperane AKA (R,R) Phacetoperane all appear to be legal BUT since the parent compound was used medically, at least we have data on that and one important detail is hidden in the name. It IS only a single enantiomer. Now, chiral synthesis costs more... but they did it anyway. So why?