The Big and Bangin' Pseudo-Advanced Drug Chemistry, Pharmacology and More Thread, V.2

[LeLouche]

Figured I'd post this here.

Is there any harm to keeping CYP3A4 inhibited for long periods of time? Not taking into account the pharmaceutical drugs it metabolizes

 

[Transform]

If one were trying to form a 2C-X freebase, would using NaOH lead to the possibility of nucleophilic substitution at the 4-position, destroying the compound?
EDIT: Now that I think about it, if one were to dissolve, say, 2C-I HCl in water, the chloride anion would dissociate. Could this then act as a nucleophile, leading to formation of 2C-C? Excuse my poor chemistry, but hey, that's what this thread is for!

Further, I've tried this with 2C-E and 2C-B and have been successful vaporising them,

 

[Vader]

I presume (well, I'm pretty sure) that such reactions can happen (after all, Shulgin used 2C-B as a precursor for the series), but I guess asking about under what conditions they might occur is verging on synthesis discussion. Ah, well, I'll just hit the books.

What's the logic behind the "25x-NBOMe" naming (the 25 bit, specifically)? I thought it might be the position of the methoxyl groups, but that seems odd, and those probably aren't the right numbers for those positions on those molecules. Anyway, should I be saying "two five x" or "twentyfive x"?

 

[Astavats]

It's the positions of methoxy substitutions as there is also 24-NBMeO, -NB, and -NBOH in this paper for the 2,4-dimethoxy counterparts.

 

[nuke]

Dextromethamphetamine can cross the cell membrane (due to lipophilicity) directly in the absence of a transporter and induce release

Unlikely.. It's charged at pH = 7 and also fairly large. Amphetamine uses a saturatable transporter to cross the bbb.
springerlink.com/content/g038l05313406571/

Probably the reason why beta-hydroxylated amphetamines do not cause severe intoxication is due to poor transport through the bbb, but that's a personal hypothesis. There has also been suppositions that the enhanced activity of meth compared to amp is due to enhanced lipophilicity, but i'm not sure i buy it as the pka for the amine in meth is higher (--> more likely to be charged at pH=7).

 

[sn23]

I presume (well, I'm pretty sure) that such reactions can happen (after all, Shulgin used 2C-B as a precursor for the series), but I guess asking about under what conditions they might occur is verging on synthesis discussion. Ah, well, I'll just hit the books.

Yes, let's just say that either more reactive halogen compounds or more special conditions are needed for such aromatic halogen substitutions to happen.

I assumed you meant aqueous solutions. Freebasing with molten NaOH might be another story.

 

[bluedom]

My guess is that it's just the monamine depletion that leads to breaking the neural circuitry that causes damage (like an atrophy). If you think of the monamine signal as a wire in a circuit (which is a complex feedback system) then when the wire is cut the ends are damaged and/or perhaps it's just rewiring to a new circuit.

Oh, interesting. So perhaps it's entirely thermal.

 

[Steps]

In response to an earlier post

Dopamine Reuptake Inhibitors have a tendency to produce anxiogenesis, paranoia, uncomfortable physical stimulation, diaphoresis, and such in me

Whereas Dopamine Releasing Agents have a tendency to produce anxiolysis, paranoia relief, physical stimulation that isn't uncomfortable, and diaphoresis only on the comedown

P.S., what would this do? Its kinda... a double methamphetamine

 

[sekio]

"doubled up" methamphetamines are too bulky to bind to transporters effectively.

 

[Steps]

"doubled up" methamphetamines are too bulky to bind to transporters effectively.

I dont think youve ever replied to me on AIM

anywho, eh, a nitro meth of some sorts maybe?

 

[ebola?]

Where would you want the nitrogen substitution? Ring-nitrogentation at the 4 position can be useful with psychedelic SAR (yet not particularly well plotted out in terms of receptor affinities), but n-methylation of phenethylamines tends to abolish psychedelic activity. nitrogenation elsewhere needs further explanation.

ebola

 

[Steps]

Can someone explain why 4-MAR isn't neurotoxic?

 

[sekio]

It would be expected to have a similar neurotoxicity to amphetamine, but less than methamphetamine.

The aminorexes have not been investigated too much due to unwanted 5HT2B agonism at heart valves (c.f. fenfluramine & the Fen Phen crisis).even though at first glance it seems they are "miracle stimulants".

 

[Steps]

It would be expected to have a similar neurotoxicity to amphetamine, but less than methamphetamine.

The aminorexes have not been investigated too much due to unwanted 5HT2B agonism at heart valves (c.f. fenfluramine & the Fen Phen crisis).even though at first glance it seems they are "miracle stimulants".

But, I've been reading up, and so far studies can't show any evidence of neurotoxicity, the only studies that did had to use doses high enough to kill half of the animals and make them have convulsions to cause any downregulation or neurotoxicity

 

[IBDResearch]

Can anyone read a few NMR results for me?

I recently got a few results back from the lab. I however can not read NMR results. The person who usually doe this for me is not available.

This is what the lab wrote along with the results and all four are within one PDF. I am going to try and upload the PDF which is password protected here but if it doesn't upload I will upload it using some hosting website. http://www.pdfhost.net/index.php?Action=Download&File=ea91c1835bf297450a895704bbdf0a8f The password is: 1q47iwrt7
This is the description of each one.
A2012.0001 is AH7921
B2012.0001 is 2cB-fly.
M2012.0005 is 4-meo-pcp hcl
D2012.0001 is desoxypipradrol

Thanks so much!

 

[Epsilon Alpha]

But, I've been reading up, and so far studies can't show any evidence of neurotoxicity, the only studies that did had to use doses high enough to kill half of the animals and make them have convulsions to cause any downregulation or neurotoxicity

My theory is that they lack a toxic metabolite or binding site that is responsible for amphetamine related toxicities, like NAChR or any of the random mGluR's amphetamines seem to love binding to.

 

[skillet]

I recently got a few results back from the lab. I however can not read NMR results. The person who usually doe this for me is not available.

This is what the lab wrote along with the results and all four are within one PDF. I am going to try and upload the PDF which is password protected here but if it doesn't upload I will upload it using some hosting website. http://www.pdfhost.net/index.php?Action=Download&File=ea91c1835bf297450a895704bbdf0a8f The password is: 1q47iwrt7
This is the description of each one.
A2012.0001 is AH7921
B2012.0001 is 2cB-fly.
M2012.0005 is 4-meo-pcp hcl
D2012.0001 is desoxypipradrol

Thanks so much!

The 4-MeO-PCP looks ok, maybe 50-60% pure judging by the integration between 2.2-0.9ppm. The rest are just wrong. Desoxypipradol should have a huge 10H mess around 7ppm rather than a 1-2H doublet. AH-7921 is missing an aromatic proton, and the peak at 5.2ppm shouldn't be there. 2CB-FLY I think is actually 2C-E...

Edit: D2012.0001 could be 2C-iP.

 

[DroopyEyedKoala]

The 4-MeO-PCP looks ok, maybe 50-60% pure judging by the integration between 2.2-0.9ppm. The rest are just wrong. Desoxypipradol should have a huge 10H mess around 7ppm rather than a 1-2H doublet. AH-7921 is missing an aromatic proton, and the peak at 5.2ppm shouldn't be there. 2CB-FLY I think is actually 2C-E...

Edit: D2012.0001 could be 2C-iP.

That's not sounding good... Anyone have a second opinion or is this the general consensus?

 

[atrollappears]

or any of the random mGluR's amphetamines seem to love binding to.

What?? Amphetamines bind to mGluRs?

the pka for the amine in meth is higher (--> more likely to be charged at pH=7).

Oooh interesting. Perhaps this explains some of its potency.

 

[Hyperthesis]

I recently got a few results back from the lab. I however can not read NMR results. The person who usually doe this for me is not available.

This is what the lab wrote along with the results and all four are within one PDF. I am going to try and upload the PDF which is password protected here but if it doesn't upload I will upload it using some hosting website. http://www.pdfhost.net/index.php?Act...895704bbdf0a8f The password is: 1q47iwrt7
This is the description of each one.

Skillet already summed it up nicely.
However, there came a question for a second opinion. Here it goes:

A2012.0001 is AH7921

...definitely not! AH-7921 contains a 1,3,4-trisubstituted phenyl-ring, but the spectrum rather indicates a para-substituted aromatic moiety. The resolution of the scan in the high-field (1-4 ppm) is too bad and thus lends only to speculation. And whatever that material actually is - at least it isn't pure. Impurity-peaks can be seen eg. at 1.15/1.17, ~2.3, 2.8 and 5.1 ppm. I'd think that the broad singlets at 9.2 and 9.9 ppm are not supposed to be there, too, judging from their integrals.

B2012.0001 is 2cB-fly

For sure not 2C-B-FLY, the two signals around 6.8 ppm just don't fit. But the guess towards 2C-E sounds actually not like the worst idea...

M2012.0005 is 4-meo-pcp hcl

Maaaaybe... The aromatic range suggests a para-positioned phenyl-ring, but that's it so far. Apart from this does the spectrum invite for the wildest speculation. Without further analysis (13C-NMR, DEPT135, IR, MS!!!) I wouldn't go out on a limb and confirm that this is 4-MeO-PCP. Assuming for a second that the material is actually what it was supposed to be then the purity is around 60% or less.

D2012.0001 is desoxypipradrol

Nope. Skillet beats me to it: It looks indeed very much like (reasonably pure) 2C-iP; traces of solvents can be seen at ca. 1.25 and 2.1 ppm.