Ketamine salts solubility

[simstim]

ZORO
1-(3,4,5-trimethoxyphenyl)-1-oxo-1-(2-piperidinyl)methane

I was going to draw the benzylic carbomethoxy (Bz-((C=O)-O-CH3)-R) compound, but it is a lot harder to make and requires a Parr hydrogenation apparatus with H2(g) tanks.

I would've called it mescaketobenzylpiperidine myself.

 

[Skorpio]

The phenmetrazine class tends to just be reuptake inhibitors, the bulk on the nitrogen prevents serotonin 2A activity.

 

[Skorpio]

Even though this thread has some fantastical molecules, random non-molecular drawings will be removed.

 

[simstim]

I'm going to move this into the chemical fluff thread to keep the more speculative molecule posting consolidated.

Wasn't there more speculative thread that isn't full of non sense? This thread doesn't get a lot of traffic with people who I would like opinion on this.

The phenmetrazine class tends to just be reuptake inhibitors, the bulk on the nitrogen prevents serotonin 2A activity.

Well Phenylmorpholine is to pea what phenmetrazine is to amphetamine.

Surely if the 2C series can be translated to phenylpiperazine and aminorex structures and still substitute for other psychedelics it's not impossible.

2C-B-PP - Wikipedia

en.m.wikipedia.org

2C-B-aminorex - Wikipedia

en.m.wikipedia.org

Phenylmorpholine 2c-b isn't that far removed. It might be less potent than 2c-b itself but possibly active.

 

[simstim]

Perhaps 2C-B-phenyloxazolidine is better

 

[simstim]

@Skorpio thanks for the move

 

[Skorpio]

Wasn't there more speculative thread that isn't full of non sense? This thread doesn't get a lot of traffic with people who I would like opinion on this.

Well Phenylmorpholine is to pea what phenmetrazine is to amphetamine.

Surely if the 2C series can be translated to phenylpiperazine and aminorex structures and still substitute for other psychedelics it's not impossible.

2C-B-PP - Wikipedia

en.m.wikipedia.org

2C-B-aminorex - Wikipedia

en.m.wikipedia.org

Phenylmorpholine 2c-b isn't that far removed. It might be less potent than 2c-b itself but possibly active.

Moved it here, hope it's a better fit.

The 2CB aminorex and phenylpipazerine really suss me out. I can't find a single report of their activity other than a Reddit comment that might be referring to 25B nbome. The phenylpipazerine has a citation from 1986, but i worry that it just mimics TFMPP (ie shitty anxiogenic stimulation). The phenylpipazerines seem to have a pretty fundamentally different pharmacophore than the 2CXs, and the fact that it has activity with the dimethoxy group speaks to the fact that the phenylpipazerines are fairly tolerant to modification.

N-methyl DOB was said to be greatly diminished in activity, and I would expect bulkier substituents to act similarly.

Now I would be interested in being proven wrong, as new scaffolds are exciting.

 

[simstim]

According to the 2c-b-bzp Wikipedia article 2c-b-pp doesn't substitute for tfmpp.

"while the phenylpiperazine homologue 2C-B-PP substitutes for DOM in DOM-trained rats with around 1/10th the potency of DOM, but does not substitute for TFMPP.[3]: 867–868le"

I don't think the book the reference is from is in English. I haven't found it yet.

 

[Fertile]

Phenmetrazines NEED the 3 methyl or they are metabolised right away.

The fact that the amine is secondary is actually more of a blow to 5HT2a affinity. Just look at DMBMPP (one of Nichol's works). Even with the biosteric equivalent of an ortho-methoxy benzylamine, it's affinity is about the same as 2CB., and only when the (S,S_ isomer is tested. The above compound have only 1 stereocenter, but inly 1 isomer will be active so overall, less potent than 2CB.

So better, but more subtle issues. Why would the maker of phenmetrazine include the 3-methyl, an extra stereocenter? It's simple questions that will help you work out WHY they made things harder for themselves if needs be.

 

[izo]

According to the 2c-b-bzp Wikipedia article 2c-b-pp doesn't substitute for tfmpp.

its rather lame. tfmpp was the best, rather psychedelic but bzp is a plain stimulant and i hated it. 100mg and instant headache. i heard from other who went through 1,2g (!) of bzp in one session. different blokes. me and this guy.

 

[Fertile]

Yes - the QSAR is obviously quite different. The thing about benzylpiperazine derivative is they really are novel. You don't know what else it's binding to. I mean, if you stray much off the path, you fall off an activity cliff. Note the choice of TFM. So at least they knew enough not to mess with other halides. Or maybe they did and their was some fallout.

With the market the way it is, YOU are the labrat.

 

[izo]

mcpp is touted to be rather anxiogenic. tfmpp war nice but nothing compared to a good indolealkylamine or a good mesc derivative.

 

[Fertile]

Now I read the side effects, it's not something I would contemplate. There IS a lot of fallout - the fatalities seem to cover toxicity of just about every major organ of the body. They tested it on kids... why not test it on the medicinal chemists first? THAT is the only certain way to ensure that the designer of a medicine does not get too gung-ho.

 

[izo]

there is kleferin, didnt test it but the people i gave it to loved it, but these where rather beginner druggies.

 

[izo]

all in all phenylpiperazines are usable. no use for bzp like compounds, there are so many cathinones and amphetamines out there, nobody needs such stuff. you could make NSI-189 out of it but this is also crap. snort a line and you get an instant flash for about 3-4minutes. what a nootropic wonder drug...

 

[Fertile]

Interestingly, their are some well studied scaffolds with very detailed QSAR data available making them apparently good targets. It's the synthetic complexity that has ensured that they never turned up as RCs,

Nomifensine/diclofensine are good examples. Netherlands patent NL157899B 'Werkwijze voor het bereiden van een geneesmiddel, een aldus verkregen gevormd geneesmiddel en werkijze voor het bereiden van een 4-fenyl-1,2,3,4-tetrahydro-isochinolinederivaat.' is the index patent. The N-methyl makes the class all PRODRUGS. I mean, the T½ of nomifensine is 1.5-4 hours. So for it to be usable medically and taken BID or TID, their has to be an active metabolite doing all of the heavy lifting.

Someone did write a trip report on nomifensine (they had ordered it from a library of reference compounds) and stated that it was very smooth and euphoric - more like a long-lasting cocaine than an amphetamine. You can introduce SERT - diclofensine has significant SERT activity.

For what it's worth, I think 4-(4-methylphenyl)-1,2,3,4-tetrahydroisoquinoline would be the best starting point. The p-Methyl will increase SERT activity (as is covered in the QSAR) but it will also act as a sacrificial moiety i.e. it will alter the metabolism of the drug to being almost 100% oxidation of that methyl.

I'm very keen on the use of sacrificial moieties because you don't have to worry about multiple metabolites. You will just get the -CH2OH and then the -C(O)OH which the body will salt and remove. The reason why trifluoromethyl if often used in place of a plain methyl is that it cannot be metabolised and it prevents ring hydroxylation at the ortho & para positions of the ring relative to the -CF3.

I'm sure you will note that the 2 aromatics and and the tertiary amine overlay desoxypipradrol.

 

[izo]

it was pulled of the market due abuse potential. i dont get the position and need for the aromatic amine group. dont know its this is required.

 

[Fertile]

Well diclofensine doesn't have the aromatic amine. The NL patent is also US3577424A. Only Horsht in US4153697 add that amine. If you use the first patent as your index paper, you will notice that 23 other patents reference it. Between them, they provide a thorough QSAR of the class.

The para thiomethoxy is a very potent and selective SRI and the para ethynyl is a very potent triple reuptake inhibitor. Compare to JNJ-7925476. That ethynyl REALLY works wonders for activity. I've often wondered if Shulgin made 2C-YN because he saw the JNJ papers.

That said, Shulgin was very systematic.

 

[paracelsius]

Does anyone know if 2-phenylmorpholine has any stimulant properties?

It is essentially the beta methoxy version of phenethylamine closed into a morpholine ring. This could also be seen as desmethyl phenmetrazine

Does anyone have any info?

It is a potent stimulant in rats and mice, no action in dogs and sedative in humans. It was discussed a little bit here:
https://bluelight.org/xf/threads/german-translation-help.925293/ :

"Diese Verbindung besitzt am Tetrahydro-1,4-oxazinring keine Methylgruppe. Ihre Toxicität beträgt bei subcutaner Injektion bei weißen Mäusen 350 mg/kg, bei peroraler Verabfolgung bei weißen Mäusen liegt die LD50 bei 730 mg/kg. Auch diese Verbindung wirkt bei Ratten und Mäusen stark zentralerregend, ist bei Hunden jedoch wirkungslos. Orientierende Versuche am Menschen haben ergeben, daß dieser Körper auch hier keine zentrale Erregung, sondern eher eine Sedation hervorruft. Auch diese Substanz zeigt am Blutdruck deutliche Tachyphylaxie. Die pressorische Wirkung ist etwa 500--1000mal schwächer a|s die des Adrenalins.

in english

@fertile: 'This compound has no methyl group on the tetrahydro-1,4-oxazine ring. Its toxicity when injected subcutaneously in white mice is 350 mg/kg, when administered perorally in white mice the LD50 is 730 mg/kg. This compound also has a strong central stimulating effect in rats and mice, but is ineffective in dogs. Preliminary experiments on humans have shown that this body does not cause any central excitation, but rather sedation. This substance also shows clear tachyphylaxis on blood pressure. The pressor effect is about 500-1000 times weaker than that of adrenaline.'

@paracelsius: So it is stimulant in mice and rats and sedative in humans. Quite unexpected. Because you see, actually this compound is the simple 2-phenyl morpholine, that is phenmetrazine without the 4-methyl (tetrahydro-1,4-oxazine is old (formal) name for morpholine). So one would expect it to have central stimulant effect like phenmetrazine but sedative?

 

[Fertile]

Well diclofensine doesn't have the aromatic amine. The NL patent is also US3577424A. Only Horsht in US4153697 add that amine. If you use the first patent as your index paper, you will notice that 23 other patents reference it. Between them, they provide a thorough QSAR of the class.

The para thiomethoxy is a very potent and selective SRI and the para ethynyl is a very potent triple reuptake inhibitor. Compare to JNJ-7925476. That ethynyl REALLY works wonders for activity. I've often wondered if Shulgin made 2C-YN because he saw the JNJ papers.

That said, Shulgin was very systematic.

You would have to datamine all 23 patents as well as any papers that were produced by the team(s) who developed this class but it's quite surprisingly similar to simple amphetamines. I mean the methamphetamine scaffold is in there.

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