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I Like to Draw Pictures of Random Molecules

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Solipsis said:
What do you base the notion that U-47700 is an SNDRI on? ......
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This series of compounds from this danish patent (the structure at the bottom, cf the wiki to link up). They are extremely potent SNDRI but with more NDRI selectivety (Ki-SERT = 0.37uM; Ki-DA = 0.021uM and Ki-NE = 0.0097uM) about 12,000 more potent than cocaine as NDRIs. Compare the structure to that of U4x
tstt_zps2ppkrkfb.png




Now that i have time to go through that patent again, actually the di-Chloro substitution pattern doesn't skew selectivety towards SERT as with cocaine and MPH analogs where 3,4d-Cl2phenyl or naphthyl increase SERT dramatically. That's why I thought it may be more serotonergic. But obvioulsy not. So nothing to worry about serotonergic toxicity. Assuming binding similar in both cases, it will be rather selective NDRI and not SNDRI (at least by a factor of10x !)

Notice the inverted amide and the positively charged dimethylamino on the cyclohexyl replaced by a piperidine. For transporters it doens't really matter a lot whether or not a N+ is present (it only reduce activity by 100x at most, which is still huge going say from 0.025uM to 2uM still 150x times higher than cocaine!! .. The structural, steric shape of the molecule is most critical .. but who knows until tested?


The Tramadol-like NDRI (if any as I assumed) may explain why the U4x are potentially extremely addictive : extremely potent NDRI + mu Opioid agonist= speed-ball without serotonergic. Which paradoxically will make them safer since deadly opiates-induced respiratory depression is balanced out by stim NE activity (correct me if I am wrong.

Solipsis said:
The phenol does seem like a good idea though, has it been tested?
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or better yet the methoxy that can potentially get metabolized into a phenol .. I dont think they been tested: the original patent focus more on kappa selective rather that mu so they didnt really bother wasitng time on U4x!!
 
I am pretty skeptical about all that so some peer review would be sweet but it's impressive if it's true.

N-mEthyl-1-(3-methoxyphenyl)cyclohexan-1-amine.png


Much nicer idea than O-PCM??

(8Z)-5-methyl-1%2C2%2C2a%2C3%2C4%2C5%2C6%2C7-octahydroazecino%5B4%2C5%2C6-cd%5Dindole.png


5-methyl-1,2,2a,3,4,5,6,7-octahydroazecino[4,5,6-cd]indole
 
what do you expect from the 3-brom? is it isobiosteric (is that the right terminology?) to a methoxy? (bromine size)
 
Sekio said it's supposed to be equipotent or stronger, he also said deschloro K would not be that desirable (arguable, I don't like it but others do), that fluoro would be similar to deschloro which I find absolutely not true in any way and that N-ethyl-norK might be a good place to start, but due to some fluke it's apparently not good at all. I wonder if PCM would be a rought fucking beast of a drug, I think probably and that it would linger for even longer than O-PCM (deschloro-K) would also be horrible. But I don't think PCE was not disliked?

Rhodium is supposed to have made and assayed bromo-K but I can't find particulars. If it would be great, I don't get why it's not an RC hype. If it's indeed like 2-MeO ket then nooo thank you, that was one of the worst ones of all. Just dirty and rough feeling, not that unlike deschloro-K.
If they would make fluoro-K cheap enough to just be able to dose higher it could be good as a party-style dissociative rather than for real holing, but it's unexplainably expensive.

So I think that sekio is right in saying that the 2-halo is probably important for the drunken anaesthetic magical effects (well IMO almost completely true, but deschloro-K also totally immobilizes me but I don't find it magical - tolerance issues perhaps). And it must be remembered that SAR is different than from the PCPs.
 
Would A pyranylisopropylamine (simple) be able to bind transporters/TAAR1 as a monoamine releaser or reuptake inhibitor?

Or perhaps a substituted pyranylisopropylamine in the vein of the 2Cx type or DOx type agents?


I've often wondered about fluoro/bromo/iodo/nitro/cyanoketamines myself. Assuming no release, of -CN and there shouldn't be from an aromatic nitrile, correct? owing to both its bioisosteric similarity to halides, and the carbon chain extension of an alkyl, then it might be interesting to ascertain what it does if anything, as a kind of hybrid between methylamino and halo.
 
Pyrans aren't aromatic, are they? So I'd expect 1-(2H-pyran-2-yl)propan-2-amine to be sort of like propylhexidrine/DMAA - a crappy stim, and the aromatized 2-(2-aminopropyl)pyrylium would be too charged to cross BBB.
 
I remember reading way back, that bromo-ketamine wasn't supposed to be very good, or at least a lot less potent than regular ketamine - Unfortunately I can't remember were I read it.
 
Why haven't we seen other phenmetrazine analogs, seems like the RC market goes crazy with substitutions for every other substance. Why not 2-(3-chlorophenyl)-3-methylmorpholine, 2-(3-Fluorophenyl)-morpholine, or 6-methyl-2-phenylmorpholine, or any of the other dozens of substitutions that seem to make sense? Sure, 3-FPM isn't exactly methamphetamine, but lots of people are looking for functional stims, or something like 3-FPM but a little more recreational, and the market is filled with a lot worse stims.

I don't know anything about synthesis, or phenmetrazine SAR, but surely there are plenty of analogs with potential given phenmetrazines "legendary" reputation. And honestly I really like 3-FPM, I can't dose too high, but its the first stim I've been able to take in years at all without a benzo...the kindling effect has really fucked up since smoking meth all through my teen years and speedballing through my 20's(even then I couldn't do coke without plenty of heroin on hand)...I normally can't touch stims at all without a benzo nearby, not even slightly recreational doses of dexamp or focalin.
 
Coolwhip said:
Why haven't we seen other phenmetrazine analogs, seems like the RC market goes crazy with substitutions for every other substance. Why not 2-(3-chlorophenyl)-3-methylmorpholine, 2-(3-Fluorophenyl)-morpholine, or 6-methyl-2-phenylmorpholine, or any of the other dozens of substitutions that seem to make sense? Sure, 3-FPM isn't exactly methamphetamine, but lots of people are looking for functional stims, or something like 3-FPM but a little more recreational, and the market is filled with a lot worse stims.

I don't know anything about synthesis, or phenmetrazine SAR, but surely there are plenty of analogs with potential given phenmetrazines "legendary" reputation. And honestly I really like 3-FPM, I can't dose too high, but its the first stim I've been able to take in years at all without a benzo...the kindling effect has really fucked up since smoking meth all through my teen years and speedballing through my 20's(even then I couldn't do coke without plenty of heroin on hand)...I normally can't touch stims at all without a benzo nearby, not even slightly recreational doses of dexamp or focalin.
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I'm looking at nine now, not including possibility of the sole active isomer of some. Seem like quite a few exist. Are they all really unique enough to be marketed? My experience with stims, that excludes phenmetrazines though, says no and more than half are shit anyway.

fastandbulbous said:
My teeny-weenie contribution regarding anorectic activity (which generally corresponds to stimulant properties except for large/unusual reuptake inhibitors) of phenmetrazine derivatives (in rats anyway)

2-phenyl-3-methylmorpholine (phenmetrazine)

good anorectic agent, good cns stimulant. (app more euphoric then amphetamine by injection)

2-phenyl-3,4-dimethylmorpholine (phendimetrazine)

reasonable anorectic. Partially metabolized to phenmetrazine

2-phenyl-3,5-dimethylmorpholine

rather poor anorectic. Possibly steric hinderence at active site of phenmetrazine about heterocyclic nitrogen atom

2-phenyl-3,6-dimethylmorpholine

good anorectic. not much less active than parent molecule (phenmetrazine)

2-phenyl-3-methylmorpholin-6-one

Reasonable anorectic. Short half life compared with phenmetrazine
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mad_scientist said:
For what its worth the SAR data for phenmetrazine in the patent literature suggests that the only really promising substitution on the phenyl ring is 3-fluoro, pretty much every other derivative they tried was substantially less active than phenmetrazine itself (though they didn't try 3,4-methylenedioxy iirc), but 3-fluorophenmetrazine retains similar monoamine release ratios to phenmetrazine with slightly higher potency. The 3-chloro derivative appears to be a selective serotonin releaser, but these have so far generally failed to live up to expectations as novel empathogens...
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By the way, when they say 'anorectic' effects, are they excessive even by stimulant standards for things like 3-FPM or just on par with amphetamine?
I wonder anyway how levo amph can be so physical while dex is very centrally acting. I get anorexia from dexamph only on high doses.
 
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Just on par ime if not less, I've also had PDM in high doses and although its sold as a diet pill it never kept me from eating, phentermine is a more powerful anorectic from what my mother-in-law says(she has been prescribed both as diet pills).

I wonder if there would be a way to keep the SRA activity of the 3-chloro substitution while retaining stimulant affects with a substitution on the morpholine(or lack of one, maybe remove the methyl, what does removing the methyl to do the parent compound?) in order to obtain a triple releaser. I wonder how else the affects of 2-phenyl-3-methylmorpholin-6-one differ, and what the effect of a 3-fluoro/chloro substitution would do there. Or possibly going with a benzene ring, or a methyl-ester ala methylphenidate.

But from what you've told me it seems phenmetrazine is about as good as it gets(besides maybe making it more lipophilic, but I guess trying to turn phenmetrazine into cocaine would destroy everything I like about it), and 3-FPM is close enough, and there is no obvious way to increase sero affinity without losing DA/NE.

Thank you for the answer, that was very informing.
 
Coolwhip said:
Just on par ime if not less, I've also had PDM in high doses and although its sold as a diet pill it never kept me from eating, phentermine is a more powerful anorectic from what my mother-in-law says(she has been prescribed both as diet pills).

I wonder if there would be a way to keep the SRA activity of the 3-chloro substitution while retaining stimulant affects with a substitution on the morpholine(or lack of one, maybe remove the methyl, what does removing the methyl to do the parent compound?) in order to obtain a triple releaser. I wonder how else the affects of 2-phenyl-3-methylmorpholin-6-one differ, and what the effect of a 3-fluoro/chloro substitution would do there. Or possibly going with a benzene ring, or a methyl-ester ala methylphenidate.

But from what you've told me it seems phenmetrazine is about as good as it gets(besides maybe making it more lipophilic, but I guess trying to turn phenmetrazine into cocaine would destroy everything I like about it), and 3-FPM is close enough, and there is no obvious way to increase sero affinity without losing DA/NE.

Thank you for the answer, that was very informing.
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Ah nice to know it's not necessarily that anorectic.. :)

A methylphenidate analogue exists and is called methylmorphenate (not to be confused with any morphinate), which seems like a poor name technically speaking since the phenyl ring isn't morpholinized.
I don't know if it's interesting, check the BL thread..

Assuming that something like MDPV is a "good" drug and not evil like in my opinion, are piperidine or morpholine analogues worthwhile?

Anything known about any phenethylpiperidines apart from fent precursor?
 
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mUzL1SP.png


5-(2-chlorophenyl)-6-methoxy-octahydroindolizine

Also this:
4OtIlxl.png


3a-(1-benzofuran-6-yl)-5,6-dimethyl-4H,5H,7H,7aH-furo[2,3-c]pyridine
 
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