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I Like to Draw Pictures of Random Molecules

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No, fluorines are relatively quite small and in that sense (sterically) substitute for hydrogens somewhat. But assumed that the fluorine is on a carbon.

Electronically fluorine is very negatively charged (δ-). Bound to carbon which is a little positively charged (δ+) this forms a stable, balanced covalent bond. This δ is a partial charge, not like a full (+) or (-) electron charge that makes an ion.

But nitrogen is not δ+ its moderately δ- making N-F bonds not so stable. Especially -NF2 (not Fl) which would be that much harder to make (they don't want to be together like that ;) ), and is I expect a good fluorinating agent, using any possible chance to give that fluoro in a nucleophilic attack. If not oxidative or violent like noxious or explosive.
Donating fluoros is good for making teflon but not for a drug..

The acetylthio perhaps gets thioester transfered by enzymes giving the indolic thiol... probably very nasty and may be toxic. As 4-MeO tryptamines show an ether there isn't so great for creating powerful psychedelics so it's doubtful a 4-thioether tryptamine is. But anyway that wouldn't be so metabolically problematic which is why we do see the 2C-T-x series and IIRC 5-MeS-DMT (yes https://www.erowid.org/library/books_online/tihkal/tihkal46.shtml ).

5-F-a,N,N-TMT could be good, yea.. but I have never seen a,N-N-TMT itself and have no idea if it's worth giving up half the potency for little change in effect. But yeah if a,N,N-TMT is found to be very nice and worth the hassle over aMT by all means.. :) Please if you have the awesome power to 5-fluorinate shizzle start with the proven stuff like DMT, DPT etc and clarify if 5-F-psilocin is active.. :D

Nagelfar said:
I've been wondering about the variable of entropy of binding kmol values recently in terms of how that effects abuse potential, e.g. between cocaine & methylphenidate. Is there no known predictor for such a thing besides direct observation comparing two ligands?
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Docking software?
 
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3-(dimethylaminoethyl)-6,7-methylenedioxyindole.png
 
I wouldn't really call them "fake hydrogens". Yes, they have a very small radius but that might be about it in terms of similarities. They are able to form weak hydrogen bonds due to their lone pairs, are more lipophilic than C-H bonds and they are also very electronegative. These properties have big results and consequences on molecules, both in terms of pharmacodynamics and pharmacokinetics. I'll give a few examples:

1) Trifluoroacetic acid has a sub-zero pKa (it is extremely acidic) compared to the acetic acid (which has a pKa of about 5) meaning TFA is about hundred thousand times more acidic than its non-fluorinated counterpart. This is because the fluorines are so electronegative that they are able to stabilise very well the carboxylate ion's negative charge.

2) They can have big impacts on the drug's pharmacodynamic profile. Fluoroacetate can enter the Krebs cycle as acetate and halt the cycle at one of the stages because the one of the intermediate fluorine compounds can almost irreversibly bind to an enzyme (acotinase). Norfenfluramine has different pharmacology to amphetamine, and most notably is a 5HT2b agonist whereas amphetamine is not, only due to the 3-trifluoromethyl moiety. Similarly, 4-FA has a completely different mode of action to amphetamine resulting in empathogenic effects rather than just dopaminergic stimulation. Take a look at this excerpt from Traschsel's paper on fluorine in psychedelic phenethylamines: "For example,in contrast to the psychoactive escaline (70), it was observed that its fluoroescaline (76) counterpart was almost devoidof psychoactive effects. Difluoroescaline (77), on the other hand, retained, and trifluoroescaline (78) showed increased humanpotency of escaline (70). Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and durationof mescaline (22) effects."

3) The pharmacokinetic profile of drugs can be modified with fluorine. Most notably, substitution onto an aromatic ring will increase its half life due to the electron withdrawal of fluorine decreasing the ring's ability to act as a nucleophile and form epoxides.

With this in mind, O-F bonds very reactive. Sekio mentioned this compound: https://en.wikipedia.org/wiki/Trifluoromethyl_hypofluorite. The only reason it is stable I would speculate is because the TFM group withdraws electron density from O-F, stabilising it. Other compounds which aren't so lucky are extremely reactive (e.g. https://en.wikipedia.org/wiki/Dioxygen_difluoride). That being said, I would say N-F bonds would have the same problem; there's too much electron density in too little space and they just wouldn't be stable.

After a brief thought about the aMT analogue, I would most likely be active reasonable dosages and could possibly be quite potent. I'm not that well versed in tryptamine SAR to comment anymore. As for the sulphur molecule, I just skimmed the wikipedia page on organosulphur compounds and I couldn't seem to find any amide equivalents (-S-(C=O)-C-). Sulphur is a soft nucleophile and normally the carbonyl carbon of an aldehyde or ketone is a hard electrophile, which will be attacked by hard nucleophiles (small, high charge density nucleophiles), so maybe that is why we don't have sulphur equivalents of amides.

2 molecules from me:

5%2C6-methylenedioxy-2-iminoindane.png


5%2C6-methylenedioxy-2-cyano-2-chloro-indane.png
 
N-C-O's are unstable.

Imines are hydrolyzed by H2O (or saliva). So yours will be turned into:

5,6-methylenedioxy-2-oxoindan.png
 
Midnight Sun, one of your structures is alpha-PVP. I did it and liked it. Lately it has been showing up as meth on the streets.

This one was inspired by 5-MeO-DMT (obviously) and DOB:

6-Bromo-5-methoxy-3-(dimethylaminoethyl)indole.png
 
Dresden said:
Midnight Sun, one of your structures is alpha-PVP. I did it and liked it. Lately it has been showing up as meth on the streets.

This one was inspired by 5-MeO-DMT (obviously) and DOB:

6-Bromo-5-methoxy-3-(dimethylaminoethyl)indole.png
Click to expand...

Yeah I realize that, the other one next to it is plain ol' methylphenidate. Bottom one is the novelty w/ ethyl ester and the carbon chain of a-pvp bound back to the nitrogen (while maintaining geometric positioning of the amide) -- decent enough exercise in messing around with the least common denominators of DRI pharmacophores

The shitty thing about pyrrolidines is how fast they lactamize into inactive metabolites
 
Sorry, it can be hard to determine what page ppl are on here, as they come from all levels.
 
Solipsis said:
Or turns out to be sunifiram-esque? =D surprise
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well shit!

now I'm curious what just the ethylene bridge btwn the 2 nitrogens would do to u-47700 itself, anyone know if upjohn messed around with that in the patent? Suppose I should look through it when I have the time
 
Attempting a tropane-cyclized amphetamine. Amphetatropane?

AjbpH.jpg


If a charge is exchanged from one heteroatom to another (e.g. a nitro group) can two such changes exist without it being considered double-protonated or equally untenable?

For instance:

iwOss.jpg


2-beta azido-di-nitro-amino-phenyltropane
 
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