I Like to Draw Pictures of Random Molecules

[aced126]

So I was trying to make a simple dopamine releaser from one end (using phenmetrazine as the basis after noticing the phenyltropane piperidine homologues as an example of similar but with one distance of the nitrogen difference) with a dopamine reuptake inhibitor from the other (using the aforementioned PT piperidine homologue as the basis, but used the styrene length that was quite efficacious among the cocaine analogues) -

what I wound up with was looking more like an opioid, so that is how I skewed it @ the end. Hoping some residual stimulant efficacy may remain:

How would you even make that heterocycle? I'm doubtful of its stability. Surely mixing 2 different pharmacophores into one molecule is very likely to destroy both types of activity...?

 

[Incunabula]

NSFW for size. Some molecules in there, unwrap it like a christmass present for the I like to draw pictures of random molecules thread

NSFW:

2C-G3-indane (an obvious cross of jimscaline and 2C-G3. I dig the symmetry)

2C-G-1-aminoindane (looks like a spaceship Most likely unsynthable, as I understand it)

psi-3,4,5-trimethyl-phenethylamine or psi-trimethyl-2C-G (2C-G is known to be active, psi orientation aswell, unlikely that the methyl at the 5-position wil abolish activity. So I think this one actually has a chance of being interesting - nevermind the fact, that 2C-G itself already sounds awesome. I can't really recall why I didn't add an alpha methyl, making it psi-trimethyl-Ganesha. Woulda been even more cool )

could it be b/c it makes more money?..why bother going further in the synthesis. you make more dough!

Yes, absolutely. The only reason to go further in the synthesis would be, if you then made something more desireable, something better. Why spend time and money making your product subpar

 

[DotChem]

I don't think the problem with PEA is low logP (it has an alright logP, it would be lipophilic enough to pass through) but rather instead that it is pretty much a perfect substrate for the MAO enzymes. I can see how adding the cyanoethyl group increases half life of the compound in the blood, but what I don't understand is how the N-cyanoethyl group is selectively cleaved in the brain (compared to being cleaved in the stomach or elsewhere)?

You're right. LogP is not the issue with PEA but rather its metabolic stability towards MAO (both peripheral and central!). Which may help explain its short half-life in brain, blood and other tissues. If BBB transport was issue then in combination with MAO inhibitor you should be able to get decent levels in CNS. But I think it's not the case unless you dose massive amounts to overwhelm MAO which may not be a good idea!. So even you get it to the brain, it will get quickly chewed up by central MAO (at least in rats and since humans are not that different from rats!... I know a lot

Now question is: how do you get sustained CNS levels of PEA? That's I think the rational for using the 2-cyanoethyl by the authors of study. CE-PEA distribution half-life is not that different from PEA but it is a weaker MAO substrate; getting chewed up by MAO much more slowly thus releasing sustained levels of PEA. It may also be active on its own!!

Now as to how the CE is selectively cleaved off by MAOs to give PEA and cyanoacetate, we'll have to ask rats. But my guess MAO prefer less "bulky" side to chew on. So it will oxidize the carbon beta to the cyano leading to breaking off the bond....Does it make sense? But one word of caution: the study in the paper was done on R.A.T.S

now @ mentioned the diCE-P:

would be expected to have even longer half-life and sustained release of PEA.

 

[DotChem]

DARK and

DARKER

3-chlorophenyl analogues of ketamine and MXE.

HORNED DEVIL

Happy Winter Solstice 2015!

DARKEST

Dissociative opioid stims

ketamine(NMDA) + meperidine(Mu) + desmethylPiperidine(DAT)

 

[Dresden]

I dig this one

of yours, Incunabula. Particularly the way the two phenyl methoxies are sure to raise the energy or 'activity' of the otherwise indolent and greasy hydrocarbon (with one amine, so maybe I should say, 'hydrocarbonamine'). Anyway, thank you for taking the time to notice and then offer structural improvements to my very own HORNED DEVIL.

The high degree of symmetry of another one of your creations, 2C-G3-INDANE, piques my fancy as well, kind of like this 2ce analogue of my imagination:

It looks like a 2C born with two penises or something.

 

[Incunabula]

Thanks Yes, my psi-trimethyl-2C-G and your HORNED DEVIL do resemble each other a lot, but I did actually drew these molceules quite some time a go. I think maybe I was reminded of it when I saw your DEVIL. I have more molecules in a folder, and I'll probably post some more next time I'm bored.

 

[aced126]

I decided to propose some structures based on Amfonelic acid.

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

It is an antibiotic (topoisomerase II inhibitor) with DRI properties and a poorly understood MOA. SAR work has probably been done but none of it seems to have been published.

Amnofelic acid:

*

 

[Nagelfar]

How would you even make that heterocycle?

Shhhh... No synthesis discussion ;-P ;-j

I'm doubtful of its stability. Surely mixing 2 different pharmacophores into one molecule is very likely to destroy both types of activity...?

I gave up on the dopaminergic original thought when I aimed for the opioid structuring, but it's close to both a DRI & DRA in some regard

 

[DotChem]

 

[Nagelfar]

This looked a lot better in my sketch @ home:

(Paroxetine + Nisoxetine + esCitalopram)

I also think I used reductionism instead of inclusionism when merging them, so the prototype of above compound was in all likelihood more viable, but once I get onto a computer and use Marvin Beans I go a little wacky. ;-p

 

[Fruitofknowledge]

I thought of some good chemical structures of RC opioids and other psychoactive compounds, some of them I though up years ago are now showing up on the RC market. Imagine taking tramadol and replacing one of the nitrogens methyl groups with a phenethyl group, this modification increases potency by a factor of 8-14. Which in return would increase the Mu opioid binding and would make the new compound 0.8X-1.4X as morphine by weight, if you remove the methyl ether group it would increase the potency again by 6-10 time making it 3-4 four times stronger then heroin. Add a methyl group at the beta carbon of the cyclohexane ring would make it even stronger maybe around half the potency of fentanyl. The synthesis wouldn't be too difficult all the analogs mentioned, the normethylphenethyltramadol being the easiest to synthesize, but the number one rule in fight club is that you don't talk about fight club!

 

[Fruitofknowledge]

I thought of several dissociative and opioid aryl cyclohexylamines and dissociative diphenylethylamines like diphenidine. What program do you use to draw your molecules?

 

[roi]

MarvinSketch is good and free.

 

[aced126]

Use opsin and just name your compound, then right click the compound and select copy image address, then type

to put the picture here.

 

[roi]

CUMYL-FUBINACA/BzODZ-EPyr hybrid.

 

[aced126]

I thought of some good chemical structures of RC opioids and other psychoactive compounds, some of them I though up years ago are now showing up on the RC market. Imagine taking tramadol and replacing one of the nitrogens methyl groups with a phenethyl group, this modification increases potency by a factor of 8-14. Which in return would increase the Mu opioid binding and would make the new compound 0.8X-1.4X as morphine by weight, if you remove the methyl ether group it would increase the potency again by 6-10 time making it 3-4 four times stronger then heroin. Add a methyl group at the beta carbon of the cyclohexane ring would make it even stronger maybe around half the potency of fentanyl. The synthesis wouldn't be too difficult all the analogs mentioned, the normethylphenethyltramadol being the easiest to synthesize, but the number one rule in fight club is that you don't talk about fight club!

This is the molecule Fruit is referring to (I'm not sure what is the beta carbon on the cyclohexane):

N-phenethyl substitution increases potency in morphine by ~10 times because there is a small lipophilic pocket in the mu binding site to which the phenethyl can fit into. With tramadol the molecule has a lot more flexibility and nor(N-phenethyl)tramadol would likely not be in a good conformation for binding interactions with this lipophilic pocket. I think this goes for all open chain opioids as far as I know.

You are right, however, about removing the methyl ether group. Tramadol doesn't have much analgesic potency in itself (but more SNRI activity I believe), and the liver normally does the job anyway. Tramadol is probably intended to have the methyl group to make it a prodrug, which has advantages in its own right. It means IVing the drug and taking it by routes other than oral will be a lot less effective than oral itself. The O-methyl also aids with digestion obviously by increasing logP of the compound.

If SNRI activity is heavily impaired by O-demethylation, I would have to agree with you that it's a good substitution; tramadol in high doses can result in serotonin syndrome and/or seizures as a result of this I believe. However SNRI activity could play an important part in the overall effectiveness of the drug on life quality of user/patient. Nevertheless, a free phenolic group anyway has a very good calculated logP anyway (O-desmethyltramadol logP calculated: 2.64; tramadol logP: 3.18 ).

O-desmethyltramadol was sold as a research chemical for a while.

 

[Dresden]

2-piperonyl-pyridine (2-PP)

A bare bones MDMA and amfonelic acid inspired structure.

MethyleneDioxyAmfonelic Acid (MDAA)

Amfonelic acid is notoriously difficult to synthesize.

 

[roi]

Slightly reminds me of Methylone. Called Oxolinic acid, also a DRI.

 

[neurotic]

www.bluelight.org/vb/threads/502836-4-ethylmethcathinone

yeah, i saw it too but was too lazy to read it through, so had to ask got tired of your old name man?

4-MA sounds pretty scary / dangerous though, so I would want to modify a drug far away from that...

i've read that old BL thread with Erny about 4-MA too, but that's pretty much all the info i can find on it, unfortunately, and it leaves me wondering. Erny looks like he was an intelligent poster and everything, but honestly what he's mentioning i can imagine happening with MDMA, for example.

 

[DotChem]

biCoke