Obscure stimulants: Lomevactone aka DR-250

[paracelsius]

Now this compound dosent look like any stimulants whatsover .. I mean at all. A lactone with no amines whatsover let alone phenethylamine . yet it is a potent cocaine-like psychostimulants twice as potent as cocaine actually or is it methylphenidate??. French patent that one long time ago No wonder tale tale sign besides signature psychostimulants locomotor stimulation, self-admin and stereotypy: makes rats incredibly horny af (no pun intended!)... Good'day all BLighters.. Stay Safe Out There

https://en.wikipedia.org/wiki/Lomevactone

Oh btw should be perfecttly legal anywhere except UK anyway where anything that gets to the brain is banned except tea and coffee!

 

[AlsoTapered]

Researchers produced methylphenidate analogues with O in place of N and they were still active. Less so, but active. In fact, I think they replaced the N with a C and their was still some activity.

I can see that the N and O lone-pairs might allow either to produce activity but in that last case it MAY have just been the case that it just fits the receptor and produces an allosteric effect.

 

[paracelsius]

@AlsoTapered : you're right: replacing the piperidine with cyclohexyl does retain activity in the phenidate class albeit 2 order of magnitude less. then again I wonder how the heck they tested those?? logP going thru the roof terribly insoluble compounds in buffer unless they makes rats smoke it ala THC??

The N lone pair is not really involved in binding: the amine is charged at physiological pH->ammonium. rather Makes salt bridge/H-bond with a conserved Glu-COO- in all 3 transporters DAT NET SERT. Probably just entropy-driven fit receptor better .. interesting compound tho: way less toxic than the amino congenes LD0>1050mg in rats anyway!! then again, humans are not rats most of them!!!

 

[paracelsius]

One more thing I found about this interesting compound: apparently it is used as dopants in horse racing. undetectable stimulant for sure. very smart! I just dont see how any known piss test can detect that one . at least the common ELISA based tests... have to double check tho it is this compound. anybody come across any info, would appreciate. Thx

edit: Not condoning any cheating or anything but ppl are ppl?? Good'day all Blighters.. Stay Safe Out There!

 

[Rectify]

That aromatic chlorine is emulsifying. Maybe that helps the log P value.

 

[AlsoTapered]

I was always impressed by BALCO discovering that gestinone (used to treat endometriosis) could so simply be catalytically reduced to THG AKA 'the clear'.

A decade later someone in Greece evidently looked at the QSAR of anabolic steroids and produced a positional isomer, RU-2309.That would have required significantly more sophisticated synthesis but the entire Greek weightlifting team retired from the 2004 Olympics.

But since then our moderator has pointed out that their are new classes of compound that are chemically unrelated to steroids but which produce the same sort of physiological changes. I admit I was stunned because of the sheer range of compounds and recognized that an education in medicinal chemistry does NOT stand the test of time unless one is constantly reading all of the literature on the topic.

That's why I picked opioids. Their ARE some 'rules' for the QSAR but they are far, far more complex than we thought in the 1990s. Sadly almost no new research is taking place and their are some questions I recognize will never be answered. Extrapolating from incomplete data is a dangerous concept. I'm still waiting for one of those cathinones to turn out to produce an unexpected toxic effect.

 

[Tryptamite]

Any human reports online or is it that obscure?

 

[AlsoTapered]

The OP mentions a compound with three chiral centres thus EIGHT enantiomers so it's only ever going to turn up if someone with the skill-set to take the bare-bones of the patent and go through the rather lengthy and complex synthesis. It was developed by a French company so their might be an obscure publication with further data,

But safe to say, their does exist a tiny fringe of grey-market labs (like BALCO) who specialize in such products. Of course, no independent QC is carried out and of course no safety trials so nobody knows if the stuff is safe...

 

[paracelsius]

Any human reports online or is it that obscure?

So far couldnt find anything on human.. shitty thing is ppl use different development code for same molecule+common name. kind of confusing. FR did extensive animal testing (cf here ).. getting very intrigued by that compound. From that FR patent, one the few stim as close as it gets to cocaine pharmacology (2x as potent! actually). might make it my next project, who knows.. will keep posted.

The OP mentions a compound with three chiral centres thus EIGHT enantiomers so it's only ever going to turn up if someone with the skill-set to take the bare-bones of the patent and go through the rather lengthy and complex synthesis. It was developed by a French company so their might be an obscure publication with further data,

But safe to say, their does exist a tiny fringe of grey-market labs (like BALCO) who specialize in such products. Of course, no independent QC is carried out and of course no safety trials so nobody knows if the stuff is safe...

Yes and No, only 2! or rather the synthetic route gives exclusively the 3,4 trans (3RS, 4RS) no cis. There is not difference in bioactivity between the 3R, 4R and 3S, 4S. The 5-methyl makes a difference tho: The psychostimulant activity reside pretty much all in the 5R methyl. so at most you have 2 psychoactives: trans(3R, 4R)-5R and trans(3S, 4S)-5S. Incidently, the active one (5R) is crystalline solid mp ca 80oC iirc which crystallize nicely out solvent while the inactive antipode is an oil that love to stay there which makes life so much more easier for ppl on those:

A Beautiful case of the proverbial Magic Methyl that makes medicinal chemists go ahhhhhh when Nature throw in garbage all SAR QSAR AI .. or whatever tool humans come up with to predict biology: Not only the compound without the methyl is not psychostimulant (It is a sedative!!!), the position of the methyl is critical (only one enantiomer 5R is psychostimulant), and one of the compound is an oil who likes to stick around in the solvent and the other (the psychoactive psychostimulant) is solid that crystallize out. Now this is on top of the fact the compound has no positive charge whatsover and retain potent activity unlike 99.9% psychostimulants known to Humans! check out the patent: US 4287206A

Oh BTW: that wiki page that says: "only the 3R, 4R, 5R is psychotherapeutic". actually both 3R, 4R, 5R and 3R, 4R, 5S are psychostimulants..the FR were trying dissociate that with antidepressant.. even that no much difference but you need something to take to market, right?

 

[paracelsius]

That aromatic chlorine is emulsifying. Maybe that helps the log P value.

Yeah the Cl jacks up the log P (v H) makes it way too lipophilic besides not having polar groups: which is why i was wondering the only way test those in vivo is same you'd do cannabis THC: inhale unlike Bill Clinton! .. I guess other ROA will work if you can find proper solvent to dissolve the compounds..

 

[fm3]

That's why I picked opioids. (…) I'm still waiting for one of those cathinones to turn out to produce an unexpected toxic effect.

(Recreational opioid users dying by the hundreds in the background)

 

[AlsoTapered]

(Recreational opioid users dying by the hundreds in the background)

Not due to any unexpected toxicity. The side-effects of opioids have been recorded for over 2000 years and most nations have pretty robust public safety campaigns warning of those risks. If one drug is misrepresented as another, that's a different issue.

I mean compounds that are precisely what they are represented of but being novel may have unidentified toxicity.

Show me a single example of a novel opioid. Every single one that's reached the streets has come from patents and/or papers and one common factor is that they have undergone testing - you don't know if you HAVE an opioid without in vivo testing.

 

[Smyth2]

You need to see this link:

File:3,4-Diphenylpiperidines.svg - Wikimedia Commons

commons.wikimedia.org

 

[paracelsius]

You need to see this link:

File:3,4-Diphenylpiperidines.svg - Wikimedia Commons

commons.wikimedia.org

^ Nice catch! So those FR guys follow up with the lactam and the piperidine. Quite logical. Amazing how that compound is so potent as psychostimulant I mean the lactam (the one you posted). geeeezz 1mg/kg getting rats overamped running around humping!! That is like 5-10mg dose in a standard 70 kg human. Way more potent than lots of known stimulants with amines in them that I know of.

I bet you those lactams are triple reuptake inhibitor like the OP lactones but so potent it is amazing! This like 10x (meth)amph and I mean without the amino that ppl always think it is required for psychostimulants!!!. If I were in the horse racing business or olympic level sport and trying cheat I would invest money in that one. Why? they cant be detected by any known test for stimulant!!! afaik Cheating is no good. tho. But for sure they'd make nice recreational stimulants, cocaine-like for sure but that one is too potent. maybe the unsubstitued (just diphenyl lactam) more reasonable 2x cocaine. Quite fascinating compounds

I would stay away from the piperidines (I mean 3,4-diarylpiperidines) that same guys studied. Sure they are also potent psychostimulant according to those guys, but my little finger telling me they may have opioid activity (they just 4-phenylpiperidines substituted with phenyl at 3-position. I am no expert in opioid SAR but I think that position is tolerate bunch of substituents, but who knows? At the very least they would have NMDA that I am pretty sure
Thx for the references


Oh BTW: I thing the compound used in horse racing to cheat is not this or related. I think it is diphenylpiperidine aka desoxy which is kind of stupid because it lasts forever half-life is like 48 hours!!! way past racing day

Good'day All Blighters. Stay Safe Out There

 

[snmfmy]

Now this compound dosent look like any stimulants whatsover .. I mean at all. A lactone with no amines whatsover let alone phenethylamine . yet it is a potent cocaine-like psychostimulants twice as potent as cocaine actually or is it methylphenidate??. French patent that one long time ago No wonder tale tale sign besides signature psychostimulants locomotor stimulation, self-admin and stereotypy: makes rats incredibly horny af (no pun intended!)... Good'day all BLighters.. Stay Safe Out There

https://en.wikipedia.org/wiki/Lomevactone

Oh btw should be perfecttly legal anywhere except UK anyway where anything that gets to the brain is banned except tea and coffee!

These also:

Diphenyl-2-pyridylmethane - Wikipedia

en.m.wikipedia.org

Desoxypipradrol - Wikipedia

en.m.wikipedia.org

2-Diphenylmethylpyrrolidine - Wikipedia

en.m.wikipedia.org

Yes, they're attached by a shared methyl however, it's still a tri-aryl compound. The pyranone group in the op has both alkene and aromatic properties, making it tri-aryl as well.

 

[AlsoTapered]

The term 'aryl' only refers to aromatic rings. So of the above, one could be referred to as being triaryl (although counting the number of aromatics isn't often a useful way to define a compound). The other two are diaryl but also contain an alicyclic ring.

The reason we treat them differently is that the chemistry of aromatic systems is totally different to that of non-aromatics. The fact that electrons are shared between the carbons means aromatics tend to be less reactive.

There are also antiaromatics which, while cyclic and olefinic, are highly reactive. These represent one of those things that you have to learn... proceed to a higher course in chemistry to be told 'actually - their is more too it than you were taught'.