I Like to Draw Pictures of Random Molecules

[sekio]

Maybe it's a dual covalent binding agent!

 

[Nexus_Tripper]

BK-Fluoroescaline
beta-keto-4-(2-fluoroethyl)-3,5-dimethoxyphenethylamine

 

[pharmakos]

why the BK version?

also, 4-Thiomescaline is already one of the most potent 3,4,5-subbed phenethylamines. i wonder if lengthening that 4-position group will increase potency like the change from 2C-D -> 2C-E -> 2C-P. interesting idea.

 

[Nagelfar]

ACK ACK ACK

Why those functional group? It looks like a permanent poison!
Sulfonimide-ISOCYANATE ! (Really?) This looks like it instantly forms covalent binding?
Bromoacetamide moeity? (the bromo is event at the reactive alpha-position regarding the carbonyl)

Hey, I made up none of those functional groups, those were all used and published in papers in looking for a suitable antagonist to the cocaine binding site from the starting point of cocaine. I just put them together on one molecule.

...and there's nothing necessarily wrong with covalent binding. Phosphorylation causes internalization just the same in the case of substrate releasing agents, and that a neurotoxin does not make (at least in the senses that I've seen drugs deemed neurotoxic, and whatever neurotoxic effects amphetamine has at high doses I don't believe receive such appellation due to it's intended MoA as a releasing agent).

 

[Nexus_Tripper]

why the BK version?

also, 4-Thiomescaline is already one of the most potent 3,4,5-subbed phenethylamines. i wonder if lengthening that 4-position group will increase potency like the change from 2C-D -> 2C-E -> 2C-P. interesting idea.

BKs have a longer duration and lower potency. If the high potency of 2C-EF carries over to its 3,4,5 analog, this would be active in the single milligram range. The BK would make it less potent.

 

[pharmakos]

the non-beta-keto is probably going to have a really long duration already. i'd stick with the higher potency personally.

 

[roi]

3-Hydroxy-Ephenidine

Ephenidine is to diphenidine what PCE is to PCP - replace the piperidine ring with an ethyl group. I wonder if the 3-Hydroxy derivative carries any μ-opioid activity.

 

[neurotic]

SERT affinity seems to have *less* fiending than pure DAT affinity, was my thought from literature I've read. Upping SERT takes away the "more-ishness" of dopaminergics.

umm i was thinking that the simultaneous 5HT/DA release/increase was what caused the incontrollable fiendiness i.e. mephedrone and more importantly, our beloved cocaine.

DAT-knockout mice still get rewarding effects from cocaine (curiously tho, apparently they will get rewarding effects from stuff such as fluoxetine, which non-DAT-knockout mice won't get (http://www.biomedcentral.com/1471-2202/8/42))

i (a layman) always thought that it was this 5HT/DA thing that made cocaine SO fiendy. i mean, i can do methylphenidate (very dopaminergic i believe, DAT/NET affinity ratio 10 to 1, against cocaine's 3 to 5) and not redose once, and be completely fine. i can do it, get high, comedown (meh, the high is over) and i'm done. it's not unmanageable or even hard at all. but with coke it's damn near impossible (if you're snorting) and ABSOLUTELY impossible when IVing. when i'm snorting, i'm constantly thinking about the next line, and when IVing i'm only not painfully craving the next shot when i'm rushing. i always assumed this difference was due to mph's lack of serotonergic activity.

i could be wrong tho

 

[Nagelfar]

3-Hydroxy-Ephenidine

Ephenidine is to diphenidine what PCE is to PCP - replace the piperidine ring with an ethyl group. I wonder if the 3-Hydroxy derivative carries any μ-opioid activity.

....Now replace one of those phenyls back with a piperidine and you have something methylphenidate-ish.

umm i was thinking that the simultaneous 5HT/DA release/increase was what caused the incontrollable fiendiness i.e. mephedrone and more importantly, our beloved cocaine.

i (a layman) always thought that it was this 5HT/DA thing that made cocaine SO fiendy. i mean, i can do methylphenidate (very dopaminergic i believe, DAT/NET affinity ratio 10 to 1, against cocaine's 3 to 5) and not redose once, and be completely fine. i can do it, get high, comedown (meh, the high is over) and i'm done. it's not unmanageable or even hard at all. but with coke it's damn near impossible (if you're snorting) and ABSOLUTELY impossible when IVing. when i'm snorting, i'm constantly thinking about the next line, and when IVing i'm only not painfully craving the next shot when i'm rushing. i always assumed this difference was due to mph's lack of serotonergic activity.

i could be wrong tho

Perhaps, differing mechanisms of release of the NE & DAT as an adjunct to SER release together may mediate expression or pathways of certain SER receptors and not others, so thusly a SNDRI would have the inverse effect of just an SRI.

Always good to hear the appraisal of a connoisseur, however I must say. ;-j

DAT-knockout mice still get rewarding effects from cocaine (curiously tho, apparently they will get rewarding effects from stuff such as fluoxetine, which non-DAT-knockout mice won't get (http://www.biomedcentral.com/1471-2202/8/42))

The fluoxetine phenomenon may have to do with the same reason that NET will uptake DA if all of DAT has it's reuptake pumps inhibited; when the DA system is absent: NE (& by extension likely some aspects of SER) take over the neuro-physiological jobs & functions of DA; so drugs with affinity to different systems will become analogous to drugs of that 'overtaken' system.

 

[sekio]

 

[endotropic]

^do you think those will have stimulant activity? And what do you think putting the nitrogen one carbon further from the aromatic ring will do?

 

[pharmakos]

are they opioids?

 

[sekio]

top 4 are tapentadol analogues, bottom are methadone analogs.

 

[pharmakos]

i wonder how interesting a pure dextro- analogue of methadone would be as a dissociative...

 

[Nagelfar]

I'm still thinking my image at the bottom of this post has an interesting angle (pun intended) from which it is derived.

The below is taken from the idea of the HDMP-28 & DMNPC being homologues with regard to the positioning of the carbmethoxy (methyl acetate), and using the methylphenidate orientation and adding, as close to a second carbmethoxy as possible, another where it'd be in the DMNPC/phenyltropane 2-beta position orientation. Resulting in the below:

cf.:

Perhaps the whole thing could be incorporated but would the oxygen favor another spot leading to a fusion across to the benzene/phenyl in such a case or similar unstable quality? e.g.:

 

[endotropic]

top 4 are tapentadol analogues, bottom are methadone analogs.

Oh weird, u-opioid agonist NET inhibitors, I need to read more about those.

 

[sekio]

more mdone analogs

 

[pr0d1gy]

The n-methylpyrrolidine modification seems interesting. I'm going to search around and see if any analogs of tapentadol containing pyridine rather then phenol. Might such a modification enhance the SNRI properties? Also curious about substituting the alcohol for a thiol, seems pretty simple and obvious so I'm sure some literature exists.

It might be interesting to consider a in which mu activation is secondary to SNRI properties.

 

[Dresden]

bk-mescaline
4-OH-JWH-018
5-MeO-JWH-018

 

[Incunabula]

bk-mescaline

A more stimulating, longer lived and less potent mescaline? probably less stable too

I haven't tried bk-2CB myself but I don't think it sounds like the beta-keto adds anything good to 2CB at all. So yeah, besides legality I don't really see the fascination with bk'ed phenethylamines.

also, 4-Thiomescaline is already one of the most potent 3,4,5-subbed phenethylamines. i wonder if lengthening that 4-position group will increase potency like the change from 2C-D -> 2C-E -> 2C-P. interesting idea.

Yes, that is an interesting idea If that's the case, the thioethyl and thiopropyl could be as potent as many 2C's.

On a sidenote, I think the 2,4,6-pattern really hasn't got enough attention. TMA-6 held up against TMA-2 actually makes that pattern quite promising, imo.