I Like to Draw Pictures of Random Molecules

[Nicomorphinist]

From the (translated) abstract of the article "Codeonal, a Narcotic and Hypnotic" from Berliner Klinische Wochenschrift (1913), volume 49, pages 260-261:

Diethylbarbiturate is also known as barbital or barbitone.

There that article is -- that makes more sense; I think the other three codeine barbiturates were invented in the 1930s. Barbital is also used by dragon chasers, sometimes with caffeine as well, to modify the melting point of heroin, and opium ash-aspirin-barbital is a classic morning tea recipe for opium smokers . . .

Phantastica by Dr Louis Lewin, often called the father of toxicology, has a really good lowdown on the medicinal and unsupervised drugs scenes in 1920s Europe and elsewhere in the world, including some very early data on peyote, and it mentions other gnarly things like Trivalin, which was morphine valerate, cocaine valerate, and caffeine valerate mixed in a tablet.

 

[S.J.B.]

Phantastica by Dr Lewis Lewin has a really good lowdown on the medicinal and unsupervised drugs scenes in 1920s Europe and elsewhere in the world, including some very early data on peyote, and it mentions other gnarly things like Trivalin, which was morphine valerate, cocaine valerate, and caffeine valerate mixed in a tablet.

Thanks, I will have to check that one out.

 

[MmmLysergamides]

Here's a dump of some random compounds and their activity predicted by SwissTargetPrediction



2-{5,10-dioxatricyclo[7.3.0.0²,⁶]dodeca-1,6,8-trien-7-yl}ethanamine

(2-{1-azatricyclo[6.3.1.0⁴,¹²]dodeca-2,4,6,8(12)-tetraen-3-yl}ethyl)dimethylamine

5-Methyl-LSD

Lysergic Acid Ethylbutyraldehyde

4-Fluoro-DMT

17-azatetracyclo[7.7.1.0²,⁷.0¹⁰,¹⁵]heptadeca-2,4,6,10(15),11,13-hexaene

β-Cyclopropyl-Phenethylamine

β-Cyclobutyl-Phenethylamine

2,4-Dimethyl-3-phenylpyrrolidine

1-Benzyl-1-methyl-propylamine

 

[polymath]

The simple compound N,N-dimethyl-3-phenyl-1-aminopropane (probably not the correct IUPAC name) also is predicted to have affinity to both 5-HT2A and DAT...

SwissTargetPrediction

www.swisstargetprediction.ch

It's a bit difficult to believe that no one has bioassayed this before, though. It has quite obvious similarities to methadone and dextropropoxyphene.

 

[polymath]

Also, a mixed halogen version of chloral hydrate...



or nitrogen mustard...

 

[JacksinPA]

Also, a mixed halogen version of chloral hydrate...

View attachment 13619

or nitrogen mustard...

View attachment 13620

Stay away from any of the 'mustards.' They are potent alkylating agents: https://www.ncbi.nlm.nih.gov/pubmed/30834842 used as cancer chemotherapeutic agents.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs

 

[polymath]

It wasn't meant as a recreational drug, I just thought that some mixed halogen version of it could have a better selective toxicity for cancer cells vs normal ones...

 

[Nicomorphinist]

allopseudocodeine

 

[JacksinPA]

It wasn't meant as a recreational drug, I just thought that some mixed halogen version of it could have a better selective toxicity for cancer cells vs normal ones...

Can't tell from your OP.

 

[sekio]

Nitrogen mustards with 'bigger' halogen/pseudohalogen groups are even more unstable and reactive (i.e. I > Br > Cl >>> F for leaving group strength). I would be suprised if you could isolate some alpha-amino-omega-haloalkanes other than chloro cmpds... even then IIRC the tertiary "pseudo-mustard" 2-dimethylamino-1-chloropropane (used in methadone chemistry) has to be shipped and handled as the HCl salt because the freebase -N(Me)2 group wants to quaternize to an aziridine chloride badly.

Now make it go to a 5/6 member ring and change Cl to I or OTf/OTs... watch those piperidiniums pop out...


on a different tip, someone should give some bored grad students a half kilo of lysergic acid and a $50,000 merck millipore gift card and have them (after getting suitably goggle eyed on homemade LSD of course) throw a bunch of fluorination reagents at the ergoline structure. Would be neat to see, e.g. 2-fluoro-LSD, 5-fluoro-LSD, etc.

 

[blueberries]

Erm...Am I right in thinking this compound would be absolutely beautiful or not?!

I looked it up on SwissTargetPractice though and got these results:

Serotonin transporter (by homology)	SLC6A4​	P31645​	CHEMBL228​	Electrochemical transporter​	0.100578902067	490 / 0 ​
Dopamine D2 receptor	DRD2​	P14416​	CHEMBL217​	Family A G protein-coupled receptor​	0.100578902067	440 / 0 ​
Norepinephrine transporter	SLC6A2​	P23975​	CHEMBL222​	Electrochemical transporter​	0.100578902067	352 / 0 ​
Dipeptidyl peptidase II	DPP7​	Q9UHL4​	CHEMBL3976​	Protease​	0.100578902067	53 / 0 ​
Nitric-oxide synthase, brain	NOS1​	P29475​	CHEMBL3568​	Enzyme​	0.100578902067	15 / 0 ​
Nitric oxide synthase, inducible	NOS2​	P35228​	CHEMBL4481​	Enzyme​	0.100578902067	18 / 0 ​
Nitric-oxide synthase, endothelial	NOS3​	P29474​	CHEMBL4803​	Enzyme​	0.100578902067	10 / 0 ​
Serotonin 2a (5-HT2a) receptor (by homology)	HTR2A​	P28223​	CHEMBL224​	Family A G protein-coupled receptor​	0.100578902067	163 / 0 ​
Neuronal acetylcholine receptor subunit alpha-3	CHRNA3​	P32297​	CHEMBL3068​	Ligand-gated ion channel​	0.100578902067	3 / 0 ​
Serotonin 1d (5-HT1d) receptor	HTR1D​	P28221​	CHEMBL1983​	Family A G protein-coupled receptor​	0.0	37 / 0 ​
Serotonin 2b (5-HT2b) receptor	HTR2B​	P41595​	CHEMBL1833​	Family A G protein-coupled receptor​	0.0	97 / 0 ​
Serotonin 2c (5-HT2c) receptor	HTR2C​	P28335​	CHEMBL225​	Family A G protein-coupled receptor​	0.0	130 / 0 ​
Kappa Opioid receptor (by homology)	OPRK1​	P41145​	CHEMBL237​	Family A G protein-coupled receptor​	0.0	230 / 0 ​
Dipeptidyl peptidase VIII	DPP8​	Q6V1X1​	CHEMBL4657​	Protease​	0.0	48 / 0 ​
HERG	KCNH2​	Q12809​	CHEMBL240​	Voltage-gated ion channel​	0.0	45 / 0 ​
Dipeptidyl peptidase IX	DPP9​	Q86TI2​	CHEMBL4793​	Protease​	0.0	36 / 0 ​
Serotonin 3a (5-HT3a) receptor	HTR3A​	P46098​	CHEMBL1899​	Ligand-gated ion channel​	0.0	20 / 0 ​
Neuronal acetylcholine receptor; alpha3/beta2	CHRNA3 CHRNB2​	P32297 P17787​	CHEMBL2109234​	Ligand-gated ion channel​	0.0	3 / 0 ​
Cytochrome P450 2C19	CYP2C19​	P33261​	CHEMBL3622​	Cytochrome P450​	0.0	1 / 0 ​
Neurokinin 1 receptor	TACR1​	P25103​	CHEMBL249​	Family A G protein-coupled receptor​	0.0	23 / 0 ​
Thrombin	F2​	P00734​	CHEMBL204​	Protease​	0.0	16 / 0 ​
Monoamine oxidase B	MAOB​	P27338​	CHEMBL2039​	Oxidoreductase​	0.0	20 / 0 ​
Serotonin 1a (5-HT1a) receptor	HTR1A​	P08908​	CHEMBL214​	Family A G protein-coupled receptor​	0.0	155 / 0 ​
Lysine-specific histone demethylase 1	KDM1A​	O60341​	CHEMBL6136​	Eraser​	0.0	42 / 0 ​
Rho-associated protein kinase	ROCK2 ROCK1​	O75116 Q13464​	CHEMBL2111459​	Kinase​	0.0	27 / 0 ​

Absolutely no (real) opioid content...which is really fucking odd since it should be an incredible opioid; NMDA antagonist with mu, delta annd bit of SRI/ SA, maybe even a DRI and some sigma agonisn but no....Ht2a, b & c & 3a, D2, some NAch, !!KAPPA!! and a little bit of 1a to make things a bit nicer. Is this a psychedelic?! A completely out-of-the-wall, random splurge of psychedelic in a wildly opioid landscape!!

 

[Nicomorphinist]

Nitrogen mustards with 'bigger' halogen/pseudohalogen groups are even more unstable and reactive (i.e. I > Br > Cl >>> F for leaving group strength). I would be suprised if you could isolate some alpha-amino-omega-haloalkanes other than chloro cmpds... even then IIRC the tertiary "pseudo-mustard" 2-dimethylamino-1-chloropropane (used in methadone chemistry) has to be shipped and handled as the HCl salt because the freebase -N(Me)2 group wants to quaternize to an aziridine chloride badly.

Now make it go to a 5/6 member ring and change Cl to I or OTf/OTs... watch those piperidiniums pop out...


on a different tip, someone should give some bored grad students a half kilo of lysergic acid and a $50,000 merck millipore gift card and have them (after getting suitably goggle eyed on homemade LSD of course) throw a bunch of fluorination reagents at the ergoline structure. Would be neat to see, e.g. 2-fluoro-LSD, 5-fluoro-LSD, etc.

They use uracil mustards to treat some kinds of cancer -- have they found nitrogen mustards with that effect too?

This makes the list of weapons that can be used as medicines longer -- the other ploughshares beaten from swords in common use are, for example:

• Nitroglycerine and PETN, both for angina pectoris; there are soldiers, factory workers, and other people who eat C-4 (RDX), Cyclonite (RDX), and Semtex (which has both RDX and PETN) because the dizziness makes them high and presumably it is the same mechanism for the RDX
• Carfentanil is considered a Weapon of Mass Destruction
• There was a proposal in the 1960s of a similar declaration when there was some worry about the Bentley Compounds, etorphine in particular
• Then there is Kolokol-1 the Russian agent used in the theatre hostage crisis in 2002 which sounds like carfentanil and one or two other even stronger fentanils dissolved in halothane
• Radiopharmaceuticals and tracers like Caesium 137, Strontium 90, Samarium 156, and Cobalt 60 are special concerns for people purloining them and making radiological dispersion devices out of them
• Cholinergic and anticholinergic medications are weaker versions of nerve agents, BZ and Agent 15 being examples of the latter
• The organochlorine headlice killer lindane has been used in the past to spray on people in conflict situations

In the reverse, the apartheid era South African government considered using coumadin analogues, MDMA, C-Jam, methaqualone, and a number of other drugs as crowd control agents and weapons . .. they also used mixtures of two or three surgical muscle relaxants like succinylcholine and D-tubocurarine in a syringe disguised as a screwdriver on political prisoners before pushing them out of helicopters over the ocean around the country, hundreds of kilometres from land. Project Coast was what the whole thing was called.

 

[blueberries]

Welp; it seems STP can't handle metabolism :/

So what do you think of this, would it work how I think it should? Plus am I right in thinking when it splits at the amine, it'll be a racemic split between MMDA-2 and MMQ, so the dosage should be double the common dose for each (which is fairly similar), 20-30mg (so a total of 40-60mg)?
It's just unfortunate qualones don't last that long, it'll cut out halfway through the MMDA-2. However...

 

[sekio]

Welp; it seems STP can't handle metabolism :/

https://smartcyp.sund.ku.dk/mol_to_som

 

[Rectify]

Welp; it seems STP can't handle metabolism :/

So what do you think of this, would it work how I think it should? Plus am I right in thinking when it splits at the amine, it'll be a racemic split between MMDA-2 and MMQ, so the dosage should be double the common dose for each (which is fairly similar), 20-30mg (so a total of 40-60mg)?
It's just unfortunate qualones don't last that long, it'll cut out halfway through the MMDA-2. However...

I would possibly try your levo thingy. The one on the left looks dodgy to me. Just my 91 cents.

 

[Asante]

ACETAMINOFENTANYL. When Tylenol just won't cut it ^_^

Structure: para-hydroxy-acetylfentanyl or, the 4-(N-phenethyl)piperidinyl derivative of acetaminophen.

Works too, says Swiss.

.

 

[polymath]

These compounds look similar to loperamide and some of them (especially the n. 23 with R=benzyl) seem to have good affinity to mu receptors:



Is there any similarity of these with some opioid painkiller (other than loperamide) that has been in actual clinical use?

Edit: Actually, according to the article I got this from, the compound obtained from loperamide itself by hydrolysis of the amide and decarboxylation (compound 1B), is a mu receptor ligand but is only a partial agonist.

Not that it would be a good idea to try to produce that substance, some of the product could dehydrate to form something like MPTP.

 

[sekio]

Is there any similarity of these with some opioid painkiller (other than loperamide) that has been in actual clinical use?

MT-45?

 

[polymath]

Sorry for the SciHub links that required editing of the previous post... MT-45 is quite a strange opioid as it doesn't have any oxygen atoms in it. The article where they determined mu receptor affinities for loperamide derivatives (decarboxylated, amide converted to methyl ester, etc...) was not the same one where I got that table in the attached image. Opioids that are also agonists of the nociceptin receptor seem to not have the euphoric and addictive effects of morphine and other typical opioid analgesics ( https://www.ncbi.nlm.nih.gov/pubmed/30158150 ). Maybe that's why the "high" from megadoses of loperamide is so crappy.

 

[sekio]

so efavirenz sort of overlays 5-meo-dmt... hmm

i like the efavir-lsd ...