I Like to Draw Pictures of Random Molecules

[neurotic]

What about an alpha methyl homologue of that??? Seems promising enough to me. The a-methyl doesn't get in the way of psychedelic activity... (Most?) DOx are even more potent than their 2-Cx counterparts, and that beta keto group doesn't seem to get in the way of 5-HT2a agonism either (thinking of BK-2C-B... It is not a very potent drug though...)

Looks sexy too...

 

[pharmakos]

mescalone

lol'd

 

[Dresden]

Sure, you can call it whatever you want!

 

[roi]

Wouldn't bk-mescaline have a dose of like 3g+? lol

 

[sekio]

I suspect it's been made already.

 

[neurotic]

Wouldn't bk-mescaline have a dose of like 3g+? lol

the alpha-methyl could make it more potent though, if we extrapolate from the potencies of DOB (which at 1mg of the R-isomer produced a +++ according to Shulgin in PiHKAL) vs. 2C-B vs. BK-2C-B

 

[roi]

TMA is far from DOB potency, but yeah, the cathinone should definitely be much more potent than bk-mesc.

 

[Dresden]

I was thinking maybe around one gram.

 

[Nagelfar]

psychoactive (putatively) with the minty taste of camphor and vanilla.

Also comes in menthol:

Move over bromin/ketone stinky, bad taste in back of throat, chemicals. Welcome refreshing, cool breeze of that refreshing taste bud and olfactory soothing aromatically non-noxious drug.

That &:

Like I *wasn't* going to make Dimethylaminopivalophenonebenzoylmethylecgonine.

 

[Midnight Sun]

I'm one of the minority who likes dichloromethylphenidate for what it is, a long lasting super functional stimulant... the idea with the propyl ester is to make it so big and floppy it no longer hits 5HT2b. though if dichlororitalinic acid is the culprit this is kind of in vain

 

[aced126]

I'm one of the minority who likes dichloromethylphenidate for what it is, a long lasting super functional stimulant... the idea with the propyl ester is to make it so big and floppy it no longer hits 5HT2b. though if dichlororitalinic acid is the culprit this is kind of in vain

Very good idea indeed. I have a strong suspicion that the ring substituents play the major role in binding to 2b. So you're right, the alkyl group will likely reduce affinity for 2b. Although we need to compare that to reduction of DAT binding; if more affinity is lost at DAT than at 2b, it is futile. Can anyone suggest why 3,4-dcmph has a long half life compared to mph? I thought they would both undergo ester hydrolysis, which wouldn't be affected by the ring substituents would it?

 

[crmt28]

Here's a bizarre one. No idea what it will do. Very likely inactive, but it's a random molecule!

2'-Cl-3'-MeO-3-Oxa-PCP

It's supposed to look like a phenethylamine. But if you want to go even crazier with something like 2C-C:

3-Oxa-4'-Cl-2','5-DiMeO-PCP (it just rolls of the tongue!)

 

[Midnight Sun]

Very good idea indeed. I have a strong suspicion that the ring substituents play the major role in binding to 2b. So you're right, the alkyl group will likely reduce affinity for 2b. Although we need to compare that to reduction of DAT binding; if more affinity is lost at DAT than at 2b, it is futile. Can anyone suggest why 3,4-dcmph has a long half life compared to mph? I thought they would both undergo ester hydrolysis, which wouldn't be affected by the ring substituents would it?

Well, the general consensus for ring-unsubbed methylphenidate analogues seems to be that to a point, lengthening the ester increases affinity for DAT and decreases it for NET. So it should work, very well actually, because 3,4 DCMP is way too fond of NET. Furthermore the longer chain might bring potency to a more reasonable level.

as for the other question it's something I've pondered my own self... It's my guess that the 2 chlorines are interfering with hydrolysis, though I don't know how

Who was the guy who posted the MPH analogues with the piperidine ring tightened into a pyrrolidine? I liked the idea of that one...

 

[Nagelfar]

Shortened the tropane, don't know why. I think such has been shown to be ineffective.

But I wonder if this has ever been done:

EDIT:

^Someone, does the above break any rules? Would it be stable at all?

 

[aced126]

Dresden came up with pyrrolidine subbed into mph, but I'll take credit for the idea of introducing the ring into amph

Hydrolysis into 3,4-dcmph acid would terminate all CNS effects I'm guessing, but that doesn't mean the molecule can't hit the 2b receptors in the heart which arent guarded by a BBB. Nevertheless the acid would have a short half life before it's quickly excreted I think, so I would bet that even if it did have 2b affinity, it would be short lived agonism. It's pretty interesting how a tfm group in norfenfluramine increases 2b activity several fold over amph which is pretty much negligible, as well as 5ht releasing effects. I think in terms of binding interact, once the nitrogen picks up a proton it will interact with a negative residue, but an electron rich aromatic binds weakly. Once electron density is removed from the ring, better interactions will occur (ie the electron deficient aromatic repels less) and so greater 2b affinity is the result. With that being said, could one of the chlorines in the molecule be substituted with a methoxy? The idea here is to still block the transporters, but add electron density to the ring to remove 2b affinity. It'll make the ring more prone to hydroxylation but that doesn't happen anyway, so I can't comment on the new half life. As for neurotoxicity of the o demethylated metabolite, I don't think it will enter the neuron ( I don't think ritalin does anyway, correct me if I'm wrong, maybe it just doesn't block vmat 2 and agonise taar1). I think all it's gonna do is sit on the transporter and block it, and this is going to stop say dopamine entering the 5ht cell, so I guess it's similar to how fluoxetine is hypothesised to be neuroprotective post SRA administration.

 

[aced126]

Nagelfar, your first molecule could be a pretty effective reuptake inhibitor. It looks very similar to methylphenidate/methamph and is likely to bind to dat, SERT and net with reasonable comparative affinity I'd say. I wonder if replacing the oxygen with a sulphur would increase half life.

I couldn't possibly comment on whether the last molecule will be stable or not as I don't have high enough knowledge of chemistry. All I could suggest is the possibility of the double bonds attacking something positive.

 

[aced126]

Replaced chloro with fluoro to reduce clogP to 2.43 (predicted with molinspiration.com, uncertainty around +-0.5), clubcard wil appreciate lol

 

[Nagelfar]

I couldn't possibly comment on whether the last molecule will be stable or not as I don't have high enough knowledge of chemistry. All I could suggest is the possibility of the double bonds attacking something positive.

I'm using the Benzoylthiomethylecgonine (sulfur instead of oxygen) but with a hydrogen (so more, instead of less, putative electronegativity) to allow a bond both like the 3β-Alkylphenyltropane analogue 224d & e together (both have better affinities than the parent cocaine, but the latter one has better uptake selectivity and the former worse, but both are better IC50s)

 

[white55]

desmethyltriazolam - likely to be slightly less potent and longer lasting

nitrazolam - likely a good and strong hypnotic (but not crazy strong), perhaps a bit euphoric

flualprazolam - stronger and more hypnotic alprazolam, somewhere between triazolam and alprazolam imo

flunitrazolam - flunitrazepam only better, really hope they make it

pynazolam - supposedly an extremely euphoric pyrazolam analog

 

[Nagelfar]

desmethyltriazolam - likely to be slightly less potent and longer lasting

nitrazolam - likely a good and strong hypnotic (but not crazy strong), perhaps a bit euphoric

flualprazolam - stronger and more hypnotic alprazolam, somewhere between triazolam and alprazolam imo

flunitrazolam - flunitrazepam only better, really hope they make it

pynazolam - supposedly an extremely euphoric pyrazolam analog

heh, a user on WP has a personal page that, is, perhaps meant to be a list made in the future at the following link. It has those you've mentioned above. It gives pIC50 & IC50s and CAS & PubChem #s. Nice resource.