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I Like to Draw Pictures of Random Molecules

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^ It must have been a bit of work drawing all of those and making predictions...

I tried to put a non-amine version of methylphenidate, with a sulfur atom in place of nitrogen, in the Swiss target prediction app as an input (the oxygen version is known to be a likely DAT ligand). Didn't get a very high likelihood of binding to dopamine transporter. But when checking the list of similar structures it identified that with, I saw this crazy biphenyl compound that is known to inhibit both dopamine and serotonin uptake:

Compound: CHEMBL101986 - ChEMBL

Report card for Compound CHEMBL101986. C14H11ClO2, Small molecule.
www.ebi.ac.uk www.ebi.ac.uk

probably the strangest stimulant candidate I've seen...
 
Mixing Tryptamines and Dissos

5-Meo-α-3-MeoPhenyl-DIPT: C1=CC=C(C=C1OC)C(CC2=C[N]C3=C2C=C(C=C3)OC)N(CC=C)CC=C

5LMoug4.png


Mono-methylated alpha-phenylated tryptamine, a SNDRI that stands out:
N-Methyl-Alpha-Phenyl-Tryptamine: C1=CC=CC2=C1C(=C[N]2)CC(C3=CC=CC=C3)NC
DDwbWO9.png


And to reply to your Tramadol PolyMath, here's my little baby, a cocaine analog that's SNDRI and MOR(!) Perfect if you ask me.
 
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A final one for today:

I also mentioned the alkaloid epimyrtine, found in blueberries, some time about half a year ago...

imgsrv.fcgi


With its 4-piperidone structure, it could obviously be a precursor for an MPPP like drug. Putting that MPPP-like structure in the Swiss Target Prediction app didn't predict high mu affinity. but some DAT and SERT binding instead.

Leaving the propionyl ester away from that MPPP like compound gave this, where the predicted DAT binding probability is well over halfway the scale (!).

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12448
 
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Can I add it to the Gaffy's Analog act? I'll clarify it isn't my invention.
 
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Sure...

Let's call it "fenmyrtin".

Edit: Replacing the phenyl group in that compound with a 3,4-dichlorophenyl doesn't increase its likelihood of being a dopamine reuptake inhibitor, but it does make it less likely to have a cholinergic effect...

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch
 
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the knowledge that people have of chemistry on here absolutley blows my brain. i'm a simple junkie from the uk that doesn't have much of a clue about these matters. i take heroin and crack cos i like it (both) and wouldnt in a million years know the chemical composition of either crack or gear. kudos to those that do though.
 
There's also this compound lupinine, which is quite similar to epimyrtine:

en.wikipedia.org

Lupinine - Wikipedia

en.wikipedia.org en.wikipedia.org
220px-Lupinin.svg.png


Making same kind of changes (doable by oxidation, phenyl grignard) to it as I did with epimyrtine, produces these two compounds that are likely to be serotonin or dopamine reuptake inhibitors:

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12445 12446

I don't know about the rest of the world, but those lupin plants grow everywhere around here... The lupinine itself is a mild cholinesterase inhibitor, could it possibly have a nootropic effect?

Edit: Also check out the benzoate ester of lupinine. Note the 3 carbon distance between the ester oxygen and the amine nitrogen, just like in cocaine...

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12447
 
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It felt a bit unrealistic that it is this easy to draw molecules with a high probability of DA reuptake inhibition... However, even cocaine itself retains some activity after removal of the carbomethoxy group, but none if the benzoate is missing, so it may not be unrealistic that this bicyclic amine would also become a stimulant when esterified with benzoic acid.

I read the peer reviewed article about the STP application, but didn't completely get whether it actually tries to superimpose the functional groups of the estimated 3D structure on the structures of known ligands, or just checks whether the 2D version can be converted to a known ligand by addition/removal of carbons somewhere in the molecule.

Edit: Putting an amino group with N-phenyl and N-propionyl on epimyrtine did produce something with a chance of being mu agonist...

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12444
 
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^ You could probably get more reliable data by doing an actual molecular docking simulation... I'm not sure whether anyone here does drug design as a profession.

Here is a lupinine version of methylphenidate:

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12443
 
Did you see my PVP version of méthylphénidate in Gaffy's Analog Act? It's very similar to your molecule and has a great profile as well.
 
Gaffy said:
Did you see my PVP version of méthylphénidate in Gaffy's Analog Act? It's very similar to your molecule and has a great profile as well.
Click to expand...

Yeah, a similar fused ring structure...

I noticed that it's possible to copy and paste images from STP to these forum posts (at least on my Linux browser), and added some to my earlier posts.
 
A strange possible 5-HT2A agonist

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12496

The STP algorithm sees similarity to the compounds in this publication, most of which are 5-HT6 ligands but some also 5-HT2A.

www.sciencedirect.com

Structure–activity relationship of 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole analogues as 5-HT6 receptor agonists

To further investigate the structure–activity relationship (SAR) of the 5-hydroxytryptamine type 6 (5-HT6) receptor agonist 5-chloro-2-methyl-3-(1,2,3…
www.sciencedirect.com www.sciencedirect.com

Edit: And, the SwissTargetPrediction wants to draw the dextromethorphan molecule in a really annoying way, but here's DXM with two chlorine atoms (usually 3,4-dichloro increases DAT affinity) instead of methoxy group on the aromatic ring...

SwissTargetPrediction

www.swisstargetprediction.ch www.swisstargetprediction.ch

12501
 
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This is a complete shot in the dark, of course, but what I have wondered for a long time, based on the example of 2,4-dinitrophenylmorphine, where a metabolic and respiratory stimulant was glued on to morphine in Vienna in 1931 in the search for narcotics with less impact on vital signs (the same search that gave us the divine Scophedal), is there the possibility of sticking an orphenadrine molecule to morphine like that to get a stronger narcotic with built-in potentiation and anti-spasmodic and quasi-Nsaid effects without the bleeding stomach? Or naproxen or nefopam for that matter?

A drug I have heard a lot about and took a long time ago was Codeonal, which is codeine diallylethylbarbitone I think it is, it is a molecular level combination of codeine and the barbiturate Dial and was introduced in 1912 for pain with insomnia -- I've never seen the structural formula for the drug, though.
 
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Nicomorphinist said:
A drug I have heard a lot about and took a long time ago was Codeonal, which is codeine diallylethylbarbitone I think it is, it is a molecular level combination of codeine and the barbiturate Dial and was introduced in 1912 for pain with insomnia -- I've never seen the structural formula for the drug, though.
Click to expand...
From the (translated) abstract of the article "Codeonal, a Narcotic and Hypnotic" from Berliner Klinische Wochenschrift (1913), volume 49, pages 260-261:
Codeine will react with diethylbarbituric acid to form a crystallizable salt containing 63% codeine and 37% diethylbarbituric acid. This compd., however, is impracticable in the production of narcosis or hypnosis because of the large codeine content. To overcome this difficulty, a mixt. consisting of I part codeine diethylbarbiturate and 5 parts Na diethylbarbiturate was used. The com. codeonal consists of 11.76% codeine diethylbarbiturate and 88.24% Na diethylbarbiturate. This is made up into tablets each containing 0.02 g. codeine diethylbarbiturate and 0.15 g. Na diethylbarbiturate.
Click to expand...
Diethylbarbiturate is also known as barbital or barbitone.
 
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