I Like to Draw Pictures of Random Molecules

[serotoninsoldier]

4‐(5‐fluoro‐2‐methoxy‐2,3‐dihydro‐1H‐inden‐1‐yl)‐6‐
methyl‐6,11‐
diazatetracyclo[7.6.1.0^2,7.0^12,16]hexadeca‐
1(16),2,9,12,14‐pentaene

so i generated some fragments for lsd from the 5tvn pdb, then i grew that fragment until i reached this and the simulation said it had about the same affinity for 5ht2b as lsd. but idk it looks pretty bulky lol.

this one is prob better

 

[Solipsis]

Hi welcome

The diethylamide moiety plays a key role and causes exceptionally slow dissociation from 5-HT2A and 5-HT2B, so affinity is not the only thing...

Please design a selective 5-HT2A agonist haha :D - well not like NBOMe shit but selective to somehow skip 5-HT2B but not 2A... [although LSD may not be an agonist per se at 2A but a mixed agonist/antagonist there due to it's weird sticky behavior].

I guess this one is no good, probably better the oxazolidine or to constrain the oxygen onto the ergoline skeleton rather than the precious diethylamide ;D :

(8β)-6-Methyl-8-(N-ethyl-4-methyl-4-oxazolin-2-yl)-9,10-didehydroergoline

What did you simulate with?

 

[aced126]

The diethylamide moiety plays a key role and causes exceptionally slow dissociation from 5-HT2A and 5-HT2B, so affinity is not the only thing...

Source for this?

 

[Solipsis]

here, I'll google it for ya

http://www.cell.com/fulltext/S0092-8674(16)31749-4

Explains why this moiety is particularly intolerant to modification: the snagging effect / self-trapping would be delicate. Too big changes and you don't just get lower binding rates but also increased dissociation rates since the size of the group may prevent it from becoming trapped by it's own induced conformational change. My earlier wording was wrong though I think: both of those factors determine affinity?
However, I doubt that simulations can predict this trapping/snagging effect on dissociation rates so what I meant to say is affinity prediction from binding energies alone is probably not the only factor for SEsoldier

 

[WSH]

(C60-Ih)[5,6]fullerene, a doping drug for soccer players

How long do you guys think it would take until the FIFA makes this compound illegal for doping soccer players?

I've heard that both Messi and Ronaldo take this!

 

[Solipsis]

Let me just revive this classic from page 1 real quick :D

Should roll...

 

[Nagelfar]

(C60-Ih)[5,6]fullerene, a doping drug for soccer players

Nah, what's going to happen is that the Koreans (some Asian country, but I am guessing Korea, or Japan; very possibly a mainland China government Olympic "world-fair" type gimmick in near future) are going to create a nanobot foosball table; and this is going to be the actual ball

The game will be telecast through an electron microscope.

 

[Dresden]

N,N,N-tri-((indol-3-yl)ethyl)amine.

 

[Nagelfar]

Would this be a crystal salt when protonated, maybe one that sparkles? ;-j

But seriously, how would the conductive electromagnetic character of having gold metal atoms work in regard to something like a nitrogen carrying ligand substrate? Any literature to this effect? I know both chromium and rhenium work (one twice as well, one about a tenth as well, due to electro-static difference influencing their structure) on cocaine analogs. (Let's forget the multi-billion dollar/pound/euro/yuan per milligram price tag, for gold, anyway)

 

[Solipsis]

Nitrogen carrying somewhere randomly on the complex / molecule is one thing, the bond between gold and nitrogen seems like it would easily cleave the carbon-nitrogen bond and send the nitrogen off with the gold if you're not careful.

The carbon-gold complex: you need one or various coordination ligands to go with that gold... it won't do single carbon bond due to oxidation states i think. Amphetamine is way too intolerant to those kinds of modifications I think, you can't tag it so easily or if you would I think you'd rather go for the 2-position or something.

With chromium etc: that is definitely a different kind of coordination complex with cocaine - a pi-stacking one with the metal sandwiched in between some aromatic ligand, ferrocene-style... or at least pi-bound to cocaines phenyl ring on one side. So that is not normally bound to a phenyl ring but coordinated from the side because of the pi-electron cloud...

You could try something similar with chromium sort of transition metals, but I don't think gold tends to be bound that way ^ my guess is that it is just too big and the charge too spreaded or something, for that.

Just thinking out loud, i don't think i finished coordination chemistry iirc.

 

[sekio]

Yeah, the chromium/rhenium complexes are "half-sandwich" (maybe "open faced sandwich"?) compounds where the metal center "sits" on top of the phenyl ring, like an egg on toast. There's no direct sp3 bonding going on like the stuff Nagelfar depicted with the C-Au and N-Au bonding.

You might be able to make a complex from a gold(II) atom and a pair of 4-thioamphetamines minus the S-protons (deprotonated version of 4-SH-amphetamine, desmethyl-4-MTA) though.

 

[Nagelfar]

You might be able to make a complex from a gold(II) atom and a pair of 4-thioamphetamines minus the S-protons (deprotonated version of 4-SH-amphetamine, desmethyl-4-MTA) though.

Would, being a pair, it function as a dimer and be virtually non-functional until metabolization, then?

below: W/O the OTf bracketing it all (have to learn to make that in chemicalize):

^Though, the inhibition binding of the MPH/cocaine reuptake site and the substrate site are probably sufficiently different, that's why Rhenium and not Chromium, should still fit, being bigger, if it still works properly, I'd like to see this tried.

 

[JK25]

This is the official been-up-tweaking-for-two-days-and-though-a-methylenedioxy-ring-on-everything-would-make-a-better-drug thread.

Please put your pretty pictures in here and talk about them so that they do not clutter the rest of the forum.

Imagine how complex and big the molecular structure of only 1 entire human being must look like. From head to toe. I mean starting from the point of the first piece of the first part of the first piece of cell-membrane of the first cell on the longest hear to the last point of the last piece of cell-membrane of the last cell on the last toenail.

 

[Nagelfar]

Apparently trithiapentalene has a 'Pimentel–Rundle three-center' resonance model and a "10-π aromatic structure" similar to naphthalene. So seeing as the N-desmethyl, 2-acyl, 3-naphthyl is the most potent phenyltropane known, how would the above work?

 

[DotChem]

Pramipexotamine : D2R agonist + SDNRI Reuptake Inhibitor + SDNRA Releaser ..

may be Amphetaxole; AMPH+Pramipexole or Amphetazole : sounds more correct since technically it is an azole. I Wonder why Prami is called Pramipexole and not Pramipazole since it is a benzothiazole. May be trade name by original makers for marketing purpose (sounds nicer!..

 

[Dresden]

 

[Solipsis]

https://en.wikipedia.org/wiki/3-Methylamphetamine

3-Methylamphetamine (3-MA; PAL-314) is a stimulant drug from the amphetamine family. It is self-administered by mice to a similar extent to 4-fluoroamphetamine and has comparable properties as a monoamine releaser,[1] although with a more balanced release of all three monoamines, as opposed to the more dopamine/noradrenaline selective fluoro analogues.[2]

3-Methylamphetamine has been investigated for military and para-military use as a less-lethal psychochemical weapon.[3]

might be a bit too close to 4-methylamphetamine for my taste

I wonder how much 'psychochemical' weapons have ever been used?

 

[Midnight Sun]

get to it, china
there's something for everyone in the nitazene class

 

[Pomzazed]

Change that fluorophenylmethyl group to fluorophenylketo, or alike for additional CB1 activities

 

[Midnight Sun]

Change that fluorophenylmethyl group to fluorophenylketo, or alike for additional CB1 activities

supposedly linking the two ring systems with a carboxyl only serves to increase opioid potency on these... although, was putative CB1 activity ever investigated at the time -- probably not...

good eye -- the similarities between cannabinoid ligands and some opioids I have always found fascinating