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Ketamine salts solubility

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What happens if you try making an LSD analog that has a bigger molecule than an Azetidine ? Such as Lysergic Acid Diethylpyrrolidine ? Would the molecule just be inactive ? Or would it still have an effect ?
 
I came up with a new drug design. You replace the Aziridine with a Methylene Dioxy in the 2C-G-1 molecule which would make a trippier molecule closely related to MDMA. What the effects would be ? I don't know.
 
negrogesic said:
On a side note Sekio isn't a she, but do you guys remember the user Nuke from what was once known as Advanced Drug Discussion? I believe @nuke was a she.
Click to expand...

Unless sekio stated such in a public post, I will respect that person's right to remain as anonymous as they wish.
 
I'm fascinated that people believe that part of the fentanyl scaffold mated to half the MDMA scaffold seem to believe they will end up with a drug that is half-way in between.

Age 11 I had already been taught the address/message hypothesis of drug activity.

Unless they think their is a receptor that produces effects midway between fentanyl and MDMA:unsure:

Oh - and the difference between cyclohexane and benzene. I get it - they are both flat hexagons on paper... I mean, forget pi-bonds, lipophilic domains and the difference in size. THOSE are all critical as well, but if I drew the boat/chair conformations I might get accused of witchcraft.....
 
Literally been years since I've spent time dreaming up new molecules / thinking about SAR, but earlier today, this idea popped in my head. Sketched it out just for shits and giggles not thinking it would work out, but... I think we might have a winner. 🙃

 
If the biosteric volume of the adamantane fits into the receptor then the bond-angle between the aryl and the amine is correct. What's the LogP? The LogP of PCP is 4.49 so with such a bulky alkyl group, it may not cross the BBB.

Why not go for simple?

ibb.co

1 hosted at ImgBB

Image 1 hosted in ImgBB
ibb.co ibb.co

The above is in a French patent - more potent than PCP
 
AlsoTapered said:
If the biosteric volume of the adamantane fits into the receptor then the bond-angle between the aryl and the amine is correct. What's the LogP? The LogP of PCP is 4.49 so with such a bulky alkyl group, it may not cross the BBB.

Why not go for simple?

ibb.co

1 hosted at ImgBB

Image 1 hosted in ImgBB
ibb.co ibb.co

The above is in a French patent - more potent than PCP
Click to expand...
Not sure how to figure out the LogP.

Why not go for simple? I'm mostly just interested in the SAR. Not looking to find the next dissociative for the RC market. Tho I'd definitely bioassay some if ever given the chance lol.

Tried the piperidine analog, looks even more promising. If I remember the SAR differences between the n-alkyl and the piperidine cyclohexylamine dissociatives, that piperidine group helps membrane solubility significantly. Not sure if that same logic would hold for the phenyadamantylpiperidine tho.



Slightly higher probability at the opioid receptors, and of course obviously much higher at NMDAr

COC1=CC=CC(=C1)C1(C2CC3CC(C2)CC1C3)N1CCCCC1
 
It won't cross the BBB, it won't be active so unlikely to be a popular RC. Even it it were lower, that adamantane is bulky.
 
Is this a known class of compounds? Did one of my usual amateur ideas I tend to do when I'm playing around with SAR, noticed that moving that nitrogen "over" one gives a phenethylamine skeleton. First attempt showed decent transporter binding. Played around with all the obvious substitutions til I landed on this.



CNC(C)C1(CCCCC1)C1=CC=CC(F)=C1
1-[1-(3-fluorophenyl)cyclohexyl]-N-methylethanamine
LogP 3.8

The 4-trifluoromethyl has slightly better binding predicted, but a less favorable LogP, 4.47.

Lots of the other obvious substitutions one would think of for phenethylamines also work (i.e. alkyl instead of fluoro, longer alkyl groups on the "alpha" carbon or the nitrogen, removing those carbon atoms, etc). These two^ were the ones with the most favorable predictions for transporter binding tho.

4-methyl is the only substitution that adds 5-HT2a activity.



CC1=CC=C(C=C1)C1(CN)CCCCC1
[1-(4-methylphenyl)cyclohexyl]methanamine
LogP 3.81

The a-methyl analog has similar predicted binding at 5-HT2a and higher binding at the transporters. Slightly less favorable LogP, 4.04. a,n-dimethyl loses all 5-HT2a activity.

Pyrovalerone substitution lowers transporter activity, adds sigma and VMAT activity.



The SAR change in this one isn't favorable to recreational use, but still rather interesting:



Swapping the cyclohexyl ring for cyclopentyl mostly retains but reduces activity. This was the only one that seemed interesting to me, the only molecule I've found tonight that has higher predicted 5-HT2a binding than it does transporter binding.

 
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AlsoTapered said:
I don't use drugs other than those prescribed by my doctor. I'm not addicted to them although they do both produce a defined abstinence syndrome. I don't drink alcohol although I do smoke tobacco occasionally.

BUT having spent 8 years of higher education in the subject and now being severely disables does mean I have a huge amount of time to expend.
Click to expand...
It’s good to see you being productive even though you are disabled and to see you doing things by the book. My situation is not as bad as yours but I still can’t approach it with your level of virtue for lack of a better word.

I’m able bodied but live with chronic pain and 99% of my use is of legal narcotics as prescribed for about 5 years now. I would still class myself as a drug addict due to last history and cravings to let go and return to abusing Narcs.

I struggle daily with suicidal thoughts and cravings to return to the illicit drugs due to the prison ones body can be.

Do you struggle with thoughts of self destructive or hard drug abuse due to your condition? You don’t have to answer. I’m always inspired by people I meet in recovery in such situations that have the fortitude to not self destruct. I want what they have.

Except for weed I abuse the hell out of weed.
 
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LucidSDreamr said:
It’s good to see you being productive even though you are disabled and to see you doing things by the book. My situation is not as bad as yours but I still can’t approach it with your level of virtue for lack of a better word.

I’m able bodied but live with chronic pain and 99% of my use is of legal narcotics as prescribed for about 5 years now. I would still class myself as a drug addict due to last history and cravings to let go and return to abusing Narcs.

I struggle daily with suicidal thoughts and cravings to return to the illicit drugs due to the prison ones body can be.

Do you struggle with thoughts of self destructive or hard drug abuse due to your condition?

Except for weed I abuse the hell out of weed.
Click to expand...

Drugs are a temporary solution to a long-lived problem.
Suicide is a permanent solution to temporary problem.

I've watched someone die as their kidneys failed. So I stay alive because should a severe head injury occur, At least I can give others the chance. Heart, lungs, kidneys, eyes and so forth. Suicide means an inquest so those organs help nobody.

BTW Why are you moving the amine away from the aryl moiety? Note dizocilpine, the prototype NMDA antagonist or diphenidine. Their has to be an aryl just 1 methylene from the aryl. Identify the key moieties and consider their spatial relationship (including the N:).

The first effort was so close - just the LogP which, BTW, you could have brought down by adding a ketone. Where? Dunno.

pubchem.ncbi.nlm.nih.gov

1-(3-Methyl-4-thiophen-2-ylthian-4-yl)piperidine

1-(3-Methyl-4-thiophen-2-ylthian-4-yl)piperidine | C15H23NS2 | CID 15408084 - 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 pubchem.ncbi.nlm.nih.gov

Follow the patents - voila, 78 NMDA antgonists/DRIs.
 
AlsoTapered said:
Drugs are a temporary solution to a long-lived problem.
Suicide is a permanent solution to temporary problem.

I've watched someone die as their kidneys failed. So I stay alive because should a severe head injury occur, At least I can give others the chance. Heart, lungs, kidneys, eyes and so forth. Suicide means an inquest so those organs help nobody.

BTW Why are you moving the amine away from the aryl moiety? Note dizocilpine, the prototype NMDA antagonist or diphenidine. Their has to be an aryl just 1 methylene from the aryl. Identify the key moieties and consider their spatial relationship (including the N:).

The first effort was so close - just the LogP which, BTW, you could have brought down by adding a ketone. Where? Dunno.

pubchem.ncbi.nlm.nih.gov

1-(3-Methyl-4-thiophen-2-ylthian-4-yl)piperidine

1-(3-Methyl-4-thiophen-2-ylthian-4-yl)piperidine | C15H23NS2 | CID 15408084 - 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 pubchem.ncbi.nlm.nih.gov

Follow the patents - voila, 78 NMDA antgonists/DRIs.
Click to expand...
Were you ever a bona fide drug addict or some kind of recreational user? Is this the main area of pharmacology you are interested in? Or is it just one of many different areas that you research with your time? Is it just pharmacology related to recreational drugs/narcotics you like or all of neuropsychopharmacology?


I’m wondering because it seems like most people that end up interested in this niche have a drug” “abuse” history. I understand some people take a subset of these drugs (ie opioids) for non recreational purposes and maybe that’s you so that’s why you were drawn here.

Re the solution to problems quotes you mentioned….that outlook does speak to the fact that you’re not an addict. All an addict cares about is solving the current problem by whatever means needed (drugs or suicide) without considering the future at all.

I don’t agree that suicide is a solution to a temporary problem in all cases. If it really is something permanent the person is trying to escape…well it’s only temporarily in the sense that it ends when they die naturally, so what’s the difference of dying sooner besides the organ donation issue you mentioned ?
 
It was my field in further education.

I don't have anything else I can so,

And HOPE, everyone's 'choices' are half chance so whatever today threw at you, tomorrow might be better.

The vast MAJORITY of the world's population would laugh at how petty our problems are. Many don't even posses the very bottom rung of Maslow's hierarchy of needs:

Air
Water
Food
Heat
Clothes
Urination
Excretion
Shelter
Sleep

Security and safety are what they dream of. So in truth, we still 'won the birth lottery'.

And drugs? I couldn't afford weed. I can barely afford to eat. But tomorrow might be better,
 
AlsoTapered said:
It was my field in further education.

I don't have anything else I can so,

And HOPE, everyone's 'choices' are half chance so whatever today threw at you, tomorrow might be better.

The vast MAJORITY of the world's population would laugh at how petty our problems are. Many don't even posses the very bottom rung of Maslow's hierarchy of needs:

Air
Water
Food
Heat
Clothes
Urination
Excretion
Shelter
Sleep

Security and safety are what they dream of. So in truth, we still 'won the birth lottery'.

And drugs? I couldn't afford weed. I can barely afford to eat. But tomorrow might be better,
Click to expand...

But what I’m asking is if you chose that specific niche in higher education due to prior recreational drug use or that’s just the lab you got the best possible spot in or something like that, while having had no interest or prior experience with drugs recreationally or addiction wise

As far as my only problem goes,
I wouldn’t say physical pain is any easier to feel whether you’re as rich as Bezos or feeling it on the floor of a hut in rural Afghanistan with 30 cents to your name….then again if you’re in rural Afghanistan there are endless fields of opium growing on the ground so maybe it’s a little easier there.

Anyways,
I admire your positive attitude in the face of heavyproblems, in fact I’m somewhat jealous of it.
 
No - as a teen a close friend developed schizophrenia. He had used a lot of drugs. But in truth, I don't think drugs were the problem, they were self-medication. A huge series of bad things all happened to him in just 1 week: So I wanted to understand
the disease and to improve outcomes.

But some life stuff got in the way.

So Id this - the closest I can get to using my skillset.
 
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