I Like to Draw Pictures of Random Molecules

[sekio]

That looks almost like resveratrol or pinosilvin, what is it supposed to do?

 

[Pomzazed]

first one is a hydrolysable prodrug of methoxy-amnepthamine
second one is a hydrolysable prodrug of a 4F-pentylcathinone
third is a hydrolysable prodrug of THC analog (replacing OH with NH2 retains equipotent activity, one methylcyclohexylethyl is for hydrophobic bulk pocket, another is a "tail"

fourth is similar to third, but the hydrophobic bulk has extra OH there (like HU-243) and a pi-stack from that benzene, other tail has phenylnitrile where the cannabinoid "tail" like a EWG there
(eg. a bromo or cyano analog of THC at the tail-end increase CB1 activity), although the lost of etheric O and adjacent dimethyl reduces activity

sth like this:

 

[aspiringdrugdesign]

I like the hydrolysis prodrug ideas Pomzazed! That's pretty cool. They hydrolyze to carboxylic acids or amides, right?

THC analog with possible opioid activity unless my reasoning is faulty.

Has this been done before?

 

[Pomzazed]

Be worried if it will be opioid more than if it will be a cannabinoid then...
The cannabinoid "tail" position can tolerate much more change, size and functional-group wise!
And well yes basic groups have been tried there, like hydrazide in 83,84 or tertiary amine in 85,88

 

[aspiringdrugdesign]

Oo, that's a little exciting to see 88. I wonder if that cyclization is what gives it its affinity, or the tertiary amine in that position. Too bad they didn't make a version of 85 without the amide carbonyl.

Is there any info on the opioid affinities of those groups?

 

[Pomzazed]

I am not keen about opioids SARs, not much into it. Better wait for opinion from people who are in the field for more correct answer.

For things i can answer:
I wonder if that cyclization is what gives it its affinity, or the tertiary amine in that position

Cyclic or not, doesnt matter much, and

No, you just need a hydrophobic bulk along the tail length (the 1' position can be an etheric O without loss in affinity)
If the tail length is 1-3 atoms in length, it will bind but will be an antagonist
4+ atoms are agonists, >8 decreasing affinity and >10 is devoid of activity.

Electron withdrawing group (via SIGMA bond) at the tail end increase affinity
(eg. compare -CH2Br with plain -CH3)
at here N and O acts fine as withdrawing group in this manner, looking at high EN value, and not acting as donating group like via PI bond

Making it more polar, eg. 81, is ionizable at physiological pH, reduces affinity, but still able to bind
I believe an N there will make in to ammonium in bodypH, so it reduces aff. but since it is also a strong sigma- EWG so we get quite some aff. back too.

 

[llaredda]

to what degree of accuracy can you do this? generally, im great with my numbers, however, i cant picture a molecule or how where to set the orbit of the electron and shit. could always lookup a generic pic, but that pic didnt come from someone drawing it like you do... i have to guess.. you get your shit. if you were able to by chance, picture and draw dexamp, levamp, and temazepam, it would likely help me understand a little better why it works so well, and how to maximize beneficial effects and minimize the crap. i am artistically challenged so to speak . need the artsy smart type to draw their interpretation, itl help me make sense of my medicines . edit . divalproex sodium (valproic acid/epival) im iffy on that one

 

[llaredda]

am i wrong if i say i saw RLS releif AND some type of ADHD relief? i tend to be good at math, but when i was in school, i didnt make a point to learn my chemistry, so ive got some learning to do... basically to me, that almost looks like a mix of an amphetamine style drug, and an opoid style drug. if i am painting the wrong picture, please tell me, because a deeper understanding of the chemistry can be ultimetely beneficial

 

[aspiringdrugdesign]

Pomzazed, is there an upper limit to how much electronegativity at the end increases the affinity? Could you have multiple EWGs and have them mostly stack in effect?

 

[Pomzazed]

picture a molecule or how where to set the orbit of the electron and shit.

I think of them like picture with some hotspot for specific things arranged in 3D space, where "free pockets" are limited in space by various size. No, not accurate like a computer simulated model but can give a rough picture.
Secondly and sadly i cannot imagine why specific drug works so well, living things are much more complicated than "Oh, this molecules fits to this site best!". My imagination meets an end at macromolecule scale or polymers.

If you are mathman (respect you, i admit i hate calculations but i like the beauty of math), I can simplify what I think in this image. You'd get it instantly.

Just the distance d is not measured in SI nor angstrom unit in my head. It is the size of the "lego block" (eg. standard lego block is CH2 with certain size, some blocks are larger than other)

in actual i thought of more types of "nodes" than hydrophobic or philic, like H donor or acceptor, or some part prefers aromatic, or some part which prefers certain shape or size.
hardest thing to imagine is when the molecules wiggle (which they do), my brain runs out of ram to simulate after the system got large enough

 

[Pomzazed]

Pomzazed, is there an upper limit to how much electronegativity at the end increases the affinity? Could you have multiple EWGs and have them mostly stack in effect?

Interesting question, and i don't know the answer on that. I guess it can relate back to how much electronegative the tail is.
Multiple halogens, like -CF3 tail end works, and EWG in position not at the tail end also works eg -CH(NO2)-, or -O- (where it is EWG via sigma bond), or -CHF-, but is not that good unless it is 4+ or more C atoms away from the benzene ring.

I guess your perfluorinated-tail...er... "Teflonabinoids" may also work*, but the CF2CF2CF2CF3 isnt that much more electronegative than CF2CF3
(*if the fluorous phase effect doesnt yet kick in, as perfluorocarbon tends to dissolve only in itself and forms separate 'teflon' phase, away from both aqueous and oil layer)

 

[aspiringdrugdesign]

Seems like it has limiting returns then

Got a CF3 group and a sulfide instead of an ether (meant to make those wedge bonds protons, not methyls)

 

[Hodor]

am i wrong if i say i saw RLS releif AND some type of ADHD relief? i tend to be good at math, but when i was in school, i didnt make a point to learn my chemistry, so ive got some learning to do... basically to me, that almost looks like a mix of an amphetamine style drug, and an opoid style drug.

Which picture were you referring to?

 

[Volsam]

Its been awhile since the last post and I like reading this thread when I eat!...

So today I was reading about 2C-B-Ind and hypothesized a few molecules in my mind. Given the fact that 2C-B-Ind was rather weak as a psychedelic, I though changing the 4 position to propyl might change that to a more favorable effects/side-effects ratio.

Also, would a benzofuran analog of it be active at all?

And what about these guys? :D

Then I also thought of 2C-D's difurans analogs (obviously inspired by a crazy weird 2C-B-Fly), do you guys think that unsaturated version of that difuran can be made and what difference would it possibly have with saturated one?

Also, this weirdo -

Would it be even possible to make it and what effects do you think it would have?

 

[aspiringdrugdesign]

Why the 4-propyl?

You put a tetrahydrofuran instead of a furan (aromaticity) but it'd probably have some serotonin activity as there'd be hydrogen bonding and a tryptamine structure However, the methylamine branch instead of ethylamine branch would be problematic as it'd look more like gramine than tryptamine, which is toxic!

To see how your 2C-D analogs might be different depending on saturation, you might want to look into the differences between 2C-B-FLY and bromo dragon-FLY, although there's an alpha methyl difference between those two as well. I'm not sure if there's a 2C-B-FLY analog that has unsaturated wings other than bromo-dragonFLY.

I like your ideas!

 

[cj187]

That's an interesting idea turning the indane into a dihydrobenzofuran. Here's an analog of TMA-6 inspired by that idea:

Here's an even more constrained analog:

This one's a little goofy looking but it can be considered a constrained analog of DOM and 5-MeO-6-APB:

Here's the indane version so it's more symmetrical:

Another indane 2C-G-3 derivative:

Mescalysergide:

I was just messing around when I made that one, but then I came up with these, which I think actually have some potential. They are similar to the NDEPA series, but with an extra ring analogous to the lysergamide d-ring.

And now, a hybrid of 2C-TFM-2-dragonfly-5-butterfly-NBOMe and LSZ. Guaranteed to be the most potent psychedelic ever

 

[Volsam]

Why the 4-propyl?

Just really enjoy 2C-P so I thought propyl substitution will provide very good lipophilicity and it is heavier than Chlorine (35.4 g/mol) but lighter than Bromine (79.9 g/mol). Propyl alkyl chain being at approx 45 g/mol.

You put a tetrahydrofuran instead of a furan (aromaticity) but it'd probably have some serotonin activity as there'd be hydrogen bonding and a tryptamine structure However, the methylamine branch instead of ethylamine branch would be problematic as it'd look more like gramine than tryptamine, which is toxic!

Isn't it awesome how it is all made in nature! One carbon less in a chain that connects an dimethylamine with an indole and instead of godly DMT you get toxic Gramine!

I like your ideas!

Thank you much, I never liked (or rather never wanted to understand) chemistry (although always liked biology and physics) until I started trying drugs...8)


cj187, I really like your indane structure, I'd try it just because it looks so deliciously good and symmetrical!
The goofy amphetamine version is probably going to be a neat empathogen but its my wild guess...

I wonder if your Mescalysergide would show activity, looks good!..
NDEPA variations also intriguing! (thanks for the link btw!)

The last one is a pure craziness but I get the humor - put all most potent known psychs in one! 8(



Drawing drugs is fun, for those wanting to try for the heck of it, there is emolecules.com - I love doodling there! :D

 

[Jabberwocky]

Psychotridine is one crazy looking molecule:

Psychotridine: https://en.wikipedia.org/wiki/Psychotridine

Would opening those rings and methylating those amines spice things up a bit?

 

[sekio]

I thought you were joking about that structure. But it's a real thing. Wow.

Bonus points to anyone who can propose a 1 step synthesis

 

[sekio]

Are the methylene analogues of barbiturates active?