• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Cocaine Replacement

C

clubcard

Bluelighter
Joined
Apr 12, 2013
Messages
1,483
SMILES CN3[C@H]1CC[C@H]3C[C@@H]([C@H2]1)c2ccc(cc2)N(=O)=O
IUPAC (1S,5S)-8-methyl-3-(4-nitrophenyl)-8-azabicyclo[3.2.1]octane

So, here are the pluses and minuses

positive
--------

-Currently Legal
-Simple synthesis from available compounds.
-Effects and duration VERY similar to cocaine
-No Levamisole
-Stops Mexican Drugs War that has killed 120,000 people already

negative
---------

-not thoroughly tested in animal models
-Strong action and short duration due to p-nitro group that the body will reduce - aromatic amines are sometimes 'bad' i.e. mutagenic (see nitromethaqualone).
-Won't 'base' as freebase is a liquid
-Synthetic route not designed so relying on real chemists, not 'cooks'
-Synthetic route involves flammable solvents and precursor so requires a real lab, not a kitchen
-Not very soluble - the sulfate or possibly phosphate is required.


Some of the pluses might seem like minuses and vice versa but, to me, those deaths would top me using coke, even if I liked stimulants. Taking away cocaine trafficking and you will be saving 10s of thousands of innocent people.
Losing the ester reduces activity but this compound has a much higher LogP so it accumulates in the brain more than coke. It has the local anesthetic effect which makes me suggest that it shares the same risk of heart problems.

So, it's largely untested but replicates cocaine almost perfectly.

FREEDOM OF SPEECH
 
lKQEI.jpg


Here it is in 2D, cc has been going off on this one for a while now.

I'm curious as to what acetoxy (ortho, para, meta) would be best on a phenyl; the ones on the benzoyloxy all seem to make higher affinities than coke itself; the plus being a more rapid penetration and cocaine itself as a metabolite (I'm thinking). The increased NE affinity being too much is the only problem. But the para-cis-propenyl troparil comlpetely negates that; so I'm thinking, as for a plain modification (because face it, we'd have to likely get coke as a precursor itself, just keep the batch clean) and perhaps, di-(2′-6′)-ortho-acetoxy-para-cis-propenyl-phenyltropane would be a great chance at something that hits harder than coke itself.
 
Err... the link between the nitrobenzene and tropane-ring is the wrong isomer. Like I said, there is a chiral centre. If you think about it, it has 4 different groups on that carbon. It's just that the -H isn't shown.

Use ACD/Chemsketch or something similar & just paste the SMILES string or the IUPAC name into it for image of compound.
 
The link between the nitrobenzene and tropane-ring is the wrong isomer. Like I said, there is a chiral center. If you think about it, it has 4 different groups on that carbon. It's just that the -H isn't shown.

Use ACD/Chemsketch or something similar & just paste the SMILES string or the IUPAC name into it for image of compound.

[img]http://postimg.org/image/vz35l89n1/

Freedom of Speech
 
Yep - now draw it in ACD/Chemsketch from the SMILES or IUPAC to see the compound you want. The one chiral center IS tricky BECAUSE of how it looks when you would hand-sketch but in chemistry.

The exact free-chemdraw you get will allow you to see compound in 3D so you can take 2, 3D models and overlay to see what matches.
 
clubcard said:
Yep - now draw it in ACD/Chemsketch from the SMILES or IUPAC to see the compound you want. The one chiral center IS tricky BECAUSE of how it looks when you would hand-sketch but in chemistry.

The exact free-chemdraw you get will allow you to see compound in 3D so you can take 2, 3D models and overlay to see what matches.
Click to expand...

If only I didn't use public computers that do not allow downloads.... However, question, would the nitrogen be protonated at the para position or the usual 8-tropane? Would it make a difference? The former image has the N+, O-, would that still be the case? (the later one you had me draw doesn't have that) Of course, you said the freebase would be a liquid, so to be very proper we got an HCl in there. Also, perhaps you didn't notice, but your SMILES puts *two* double bonds, one to each oxygen on the para position. That isn't correct, is it?

3D (roughly, seeing as on a flat monitor it's always going to be "2D" in some regard, unless it is a moving image ;p )

3TNL8.jpg


LcGsr.jpg


It looks like chemicalize.org just upgraded how it depicts the π-orbital of the benzene.

Would somehow optimizing the "inductive effect" in regard to the overall structure be of benefit? I know very little but was reading into that today regarding electronegativity.

EDIT:

This is it! The ultimate cocaine analog!!!!!111

Juzw1.jpg


the oxygens in the carbmethoxy have to be changed to positronium & protonium, respectively, and the benzene replaced with a uranocene, then the eight position methyl has to have quark–gluon plasma bonded to it.

(The aforementioned immediately above this line, after the annotation of "EDIT", is entirely a facetious joke, FYI to the lay-persons out there. Those are all very exotic constituents you'd be lucky to find even at CERN)
 
Last edited:
Isn't a 2-carboxylate ester (or equivalent moiety) required for stimulant activity in tropane derivatives? That group also seems to be a feature of drugs like methylphenidate, which act very much like cocaine at DAT.
 
Isn't a 2-carboxylate ester (or equivalent moiety) required for stimulant activity in tropane derivatives?
Click to expand...

It's not, tropacocaine (des-carbomethoxy-cocaine) retains stimulant activity, although it is greatly reduced to "real" cocaine.

The sterochemistry is key, too.
 
We'll yes, sure, tropacocaine may have weak activity. But at some point there isn't much of a difference between weakly active and inactive. I'm sure there are other elements of the pharmacophore that can be removed and wouldn't be missed if you increase the dose markedly. There are many ways to construct stimulant molecules. But are there a lot of people who like tropacocaine and find it to be a useful alternative to cocaine?
 
Last edited:
The IUPAC & SMILES I provided are of the correct isomer. Losing the remaining ester increases the LogP - compounds with lower affinity can be just as active if more of it ends up in the brain. It HAS been tried by humans and everyone commented on it being identical. This isn't a guess, this is a done deal as far as activity goes.
 
Is this supposed to have mainly reuptake blocking effects? It bears a lot of structural resemblance to substitutes amphetamines except the nitrogen is tertiary.
 
serotonin2A said:
We'll yes, sure, tropacocaine may have weak activity. But at some point there isn't much of a difference between weakly active and inactive. I'm sure there are other elements of the pharmacophore that can be removed and wouldn't be missed if you increase the dose markedly. There are many ways to construct stimulant molecules. But are there a lot of people who like tropacocaine and find it to be a useful alternative to cocaine?
Click to expand...

benzoylmethylecgonine is active, benzoylecgonine is basically inactive (removing just the methyl from the carbmethoxy), benzoyltropane (removing the entire carbmethoxy, not just the methyl) is active again. One of those strange things.

BTW, on the upper left input "58" to jump to page 982 and on the right column it says "...this binding pocket was indicated to be slightly greater in diameter than a phenyl ring and was approximately 9 Å in length.". In molecular chemistry, what kind of measurement does the character "Å" indicate? I cannot find it either on WP or doing a google search.
 
neurotic said:
It's angstroms
Click to expand...

Ah, I overlooked it because it was a Scandinavian accent mark and the main WP page treated it linguistically, and the unit of length was named after a man with a Nordic surname, I glossed over it thinking it a place-name. Having a board education on many topics *can* put blinders on you when it comes to certain things, is perhaps the lesson here...
 
Sonata aka zaleplon snort it just like coke high only no numbness dont take oral you will fall a sleep fast , just tell dr u are having trouble sleeping . very crazy so much like coke have fun .f everything other is just playing with fire :)either snort coke or try Sonata you will be glad you did .
 
There are only 2 isomers and routes to produce the desired isomer. People seem to forget Singh proved you don't need the benzyl ester but https://en.wikipedia.org/wiki/3-(p-Fluorobenzoyloxy)tropane with a lower LofP and less electron-withdrawing group is active. This compound IS active as I described and samples were prepared. The only tough thing about this one is obtaining the precursor for the 1-step synthesis.
 
Jimmy000 said:
Sonata aka zaleplon snort it just like coke high only no numbness dont take oral you will fall a sleep fast , just tell dr u are having trouble sleeping . very crazy so much like coke have fun .f everything other is just playing with fire :)either snort coke or try Sonata you will be glad you did .
Click to expand...

A GABAergic? Are you trolling? ;p
 
Now, we cannot discuss synthesis BUT I think saying it's 1-step from a LEGAL precursor is possible.

I hated coke & I hate this stuff BUT I do think of the 120,000 deaths associated to gang activity. Coke is their staple, losing that market would cut into the profits SO DEEPLY. I would expect fentanyl & meth will remain their main export and now we are getting naloxone (which has a lower Ki then fentanyl) so, their won't be the death-toll. This is how it could end up low on the list of politicians priorities. Every chemist I have known who made their own fentanyl ended up with the 20-minute habit and feelings of withdrawal last for a year (not day 5, the worst, more like day 12).
 
You must log in or register to reply here.
Top