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I Like to Draw Pictures of Random Molecules

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1-phenyl-1-(2-piperidinyl)-butan-2-one.png


Ketone should still provide some (although probably a lot less than carbomethoxy counterpart) interaction with tyrosine-156? Could be a more mixed reuptake inhibitor/releasing agent? Longer half life as well as higher oral bioavailability as the ester bond previously is replaced by a C-C bond preventing hydrolysis.

Maybe probe the binding pocket more with carbons in hopes of blocking the conformational change when DAT tries to transport this molecule into the neuron. Should give more reuptake and less releasing character to the molecule as well as increase BBB penetration.
1-phenyl-1-(2-piperidinyl)-propan-2-one.png


1-phenyl-1-(2-piperidinyl)-pentan-2-one.png


1-phenyl-1-(2-piperidinyl)-4-methylpentan-2-one.png


1-phenyl-1-(2-piperidinyl)-3-phenyl-propan-2-one.png


Maybe a charged nitrogen in place of the ketone could do even better at binding to Y156.


1%2C3-diamino-2-phenyl-3-methyl-propane.png



How about locking it into 1 of the following conformations for increased (or decreased) selectivity?


5-phenyl-4-methyl-1%2C2%2C3%2C5-tetrahydropyrimidine.png



4-(1-methylaminoethyl)-1%2C2%2C3%2C4-tetrahydroisoquinoline.png


3-phenyl-2-methylpiperazine.png


Secondary amines should have maximum basicity as well so gets charged easily.
I expect the last 2 to perform reuptake the best due to the distance between the non-amphetaminergic amine and the ring (tyr residue likely to be close to the ring).
 
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is anyone able to overlay THC and JWH-018 arranged in the configuration in which they bind to the CB1 receptor? i would like to see it, but i don't have the knowledge to do so.
 

As you may recall Shulgin made and tasted N-methyl-DOB:

1-(2%2C5-dimethoxy-4-chlorophenyl)-2-methylaminopropane%20.png


He didn't explore it very much, but it didn't sound like any kind of fun at all ... he makes reference to trying some of the other halogenated versions as well ... mostly just sounds abrasive on the body, and one of the researchers had an odd experience with it potentiating psilocybin taken the day after. He doesn't say much more but it sounded like a dead end. As someone was just saying sometimes he didn't push high enough with doses but this stuff sounded physically unpleasant enough that one wouldn't want to...

Do you think that one (N-ethyl-DOC?) might be more promising?

What about using the phenmetrazine skeleton? (I bet someone has thought of this already) Too bulky?

2%2C5-DIMETHOXY-4-chloro-phenyl-3-methyl-morpholine.png


I know methylenedioxy-phenmetrazine has been discussed, wonder if anyone ever made it, and if it were active would it be MDMAish or more of a straight stimulant a la MDPV.
 
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guanidinophenylmethane.png


If this could get into the brain it could be a potent DRA as guanidines are very strong bases; it should be taken up by DAT because when substrates bind, they do so with a charged nitrogen anyway I believe. Too polar to do so probably. In an attempt to increase permeability but still be a substrate at DAT (and still be released once inside the dopamine neuron), I'll add some ring substituents. This is going to confer a lot of SERT activity as well inevitably.

methylCarbamimidoylaminomethyl(3-isopropyl-4-methoxybenzene).png


Edit: Apparently the above molecule would have a poor affinity at SERT.
 
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As you may recall Shulgin made and tasted N-methyl-DOB:

1-(2%2C5-dimethoxy-4-chlorophenyl)-2-methylaminopropane%20.png


He didn't explore it very much, but it didn't sound like any kind of fun at all ... he makes reference to trying some of the other halogenated versions as well ... mostly just sounds abrasive on the body, and one of the researchers had an odd experience with it potentiating psilocybin taken the day after. He doesn't say much more but it sounded like a dead end. As someone was just saying sometimes he didn't push high enough with doses but this stuff sounded physically unpleasant enough that one wouldn't want to...

Do you think that one (N-ethyl-DOC?) might be more promising?

What about using the phenmetrazine skeleton? (I bet someone has thought of this already) Too bulky?

2%2C5-DIMETHOXY-4-chloro-phenyl-3-methyl-morpholine.png


I know methylenedioxy-phenmetrazine has been discussed, wonder if anyone ever made it, and if it were active would it be MDMAish or more of a straight stimulant a la MDPV.

According to Shulgin n-methyl versions of 2c-x/dox are practically useless as psys. n-hydroxys are however good (think hot-7 and 2c-t-7).

There's been some talk here about using the phenmetrezine skeleton for a mdma analog.
 
white55 said:
There's been some talk here about using the phenmetrezine skeleton for a mdma analog.

So, this?

2-(3%2C4-methylenedioxyphenyl)-3-methyl-morpholine.png


Caught a bit of that discussion above. Possibly active? If the metabolism follows the same scheme as MDMA you might get some weird metabolites that might not be very active or might be surprising. TBH I would be surprised if this is not being explored unless there is a blatantly obvious reason why it shouldn't work ...

On thinking skeptically about the "psychedelic phenmetrazine" molecule I threw up in my prior post, I remembered this oddity:

1-(4-bromo-2%2C5-dimethoxybenzyl)piperazine.png


"2CB-BZP," which did in fact circulate, but nobody much liked it, it certainly wasn't psychedelic, didnt conform appropriately to 5HT2A/SERT per what I was reading. There was MDBZP, too, it was shit. I think the most people got out of them was headaches and a little stimulation. Now of course BZP isn't nearly as amphetamine like (or as good as) phenmetrazine, but both of these molecules involve largish secondary amines which I seem to recall is part of the problem? I'm an amateur, though, maybe someone else could tell me if I'm on the right track.
 
Using natural flavoring & aroma compounds seems to be a good fit to cocaine's natural skeleton for hybrids

WL35v.jpg


"Raspberry ketone"-caine.

Reminds me of Methylecgonine cinnamate, to-whit shorter and perhaps active therefore. I wonder what it's pyrolysis product may be.

1-phenyl-1-(2-piperidinyl)-butan-2-one.png


Ketone should still provide some (although probably a lot less than carbomethoxy counterpart) interaction with tyrosine-156? Could be a more mixed reuptake inhibitor/releasing agent? Longer half life as well as higher oral bioavailability as the ester bond previously is replaced by a C-C bond preventing hydrolysis.

Maybe probe the binding pocket more with carbons in hopes of blocking the conformational change when DAT tries to transport this molecule into the neuron. Should give more reuptake and less releasing character to the molecule as well as increase BBB penetration.
1-phenyl-1-(2-piperidinyl)-propan-2-one.png


1-phenyl-1-(2-piperidinyl)-pentan-2-one.png


1-phenyl-1-(2-piperidinyl)-4-methylpentan-2-one.png


1-phenyl-1-(2-piperidinyl)-3-phenyl-propan-2-one.png

The oxygen off of the carbmeth(oxy) is a good proposition, and reminds me of getting back to a MPH/fentanyl hybrid. Since there was discussion of how the benzene/phenyl can be substituted for a carbmethoxy in certain regards with specific residue binding, perhaps:

87FDO.jpg

Methylcarbmethoxylidate?
 
Yeah bagseed, as does methylphenidate eventually turn into ritalinic acid. The compound should be decent until the liver hydrolyses the ester.
 
Nagelfar, could be effective at binding but seems just way too polar to be of any use once administered in vivo.
 
What about this closed ring derivative of your reverse ester meth ace

IMG_20151103_225646.jpg


Looks a lot like pemoline, very un-innovative... Looked better in my head... How are cyclic carbamates called?

There could be a morpholinone/phenmetrazine derivative of that too... As well as ring substituted ones like 3-fluoro (phenmetrazine SAR) or 4-methyl (aminorex or amph ? SAR)
 
Do you think that one (N-ethyl-DOC?) might be more promising?

What about using the phenmetrazine skeleton? (I bet someone has thought of this already) Too bulky?

NE-DOC would hold promise only as a DOC prodrug, the tradeoff being a safer dosage (as it would be higher) for a stupidly long duration

Better idea is N-OH-DOC or N-OH-2C-X/HOT-X. Or better yet forget that DOC ever existed because it sucked. DOF-dragonfly would be interesting. DOI needs to make a comeback

I would forget the idea of phenylmorpholine based psychedelics on the presumption of half-life alone (that's assuming they even fit into 2a which I doubt)
 
I've heard really good and really bad things about DOC. Never tried any DOx personally, but hey, if DOI floats your boat, wouldn't this

1-(2,5-dimethoxy-4-iodophenyl)-2-ethylaminopropane.png


be smoother and more forgiving (especially dosage wise) than DOI. And I am not convinced N-ethyl-DOx's are prodrugs at all.

* * *

In unrelated news,

1-(2-methoxy-4-ethylphenyl)-2-aminopropane.png


and

1-(2-oxaindan-5-yl)-2-methylaminopropane.png


I call this one LOOPY (for no good reason in particular).
 
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