Novel dissociative 2-(3-fluorophenyl)-2-(propylamino)cyclohexanone

[palmanita]

Appears to be a new/rare one, PubMed and Google found nothing.
Any infos are of interest, especially from the specialists - what might its properties be, if you guess based on the structure? Long duration because of the N-propyl? Could the fluorine be "active" like the MeO of methoxetamine?

 

[aced126]

The N-propyl shouldn't increase its duration significantly compared to N-methyl or N-ethyl analogues. Pharmacodynamically, the N-propyl derivative of this molecule would be slightly less potent as an antagonist NMDA than the N-ethyl or N-methyl derivative (probably still within an order of magnitude though).

The fluorine should be partly bioisosteric to the Cl in ketamine, and also should increase half life very slightly compared to ketamine, especially since ring hydroxylation isn't even the primary route of metabolism. In general, I'd expect this molecule to have similar (within an order of magnitude) dosage and duration of action to ketamine.

If you are one of the first to sample this molecule, I would go from 1mg upwards, to be safe.

 

[white55]

nenk version 2

 

[Solipsis]

nenk version 2

I don't know, NENK is a bit confusing for the SAR because you'd theoretically expect it to be good... but this does in fact decent: http://www.bluelight.org/vb/threads/592033-3-MeO-PCPr
So I wouldn't be so fast..
I also wonder if 3-halo ACAs are 3-HO like. Which are said to feel opioid-like even though no activity at MOR has been confirmed for any of them afaik. Still, may be pretty smooth.
(Would depend on whether the electronegative substitution / proton accepting is the main point of that 3-position or whether the 3-HO actually is serving as donor)

How much less potent does the keto make them generally?

 

[white55]

sorry, looked to quickly and saw the f on position 2.... still 3-meo would imo be better or o-pcpr since dcfk is even weaker than o-pcm which is already too weak

i think the 2-keto doesn't reduce potency a lot.... but it dos reduce the hl... just look at o-pce

 

[Solipsis]

Hopefully they actually screened the N-ethyl vs. the N-propyl, apparently they can afford losing some potency with the N-propyl otherwise it seems like a pretty retarded choice to go with it?

This freshened me up:

NSFW:

A. noncyclic alkyl substituents: Replacement of the piperidine ring in PCP by other alkyl groups can lead to many active compounds. Removal of all N-alkyl substituents gives a compound about 1/2 as potent as PCP (1-phenylcyclohexylamine, PCA). Small alkyl substituents such as methyl and ethyl give compounds with increased potency relative to PCA. An N-methyl group gives a compound with about the same order of potency as PCP (possibly slightly lower). Lengthening the alkyl chain from methyl to ethyl increases the potency, and PCE is more active than PCP.

Further increasing the chain length to n-propyl or n-butyl leads to a decrease in potency, although the n-propyl compound is still of similar potency to PCP.

There is some evidence that smaller mono N-alkyl substituents such as methyl or ethyl lead to compounds with increased tendency to produce nausea. Additionally, the freebase of these analogs has a very unpleasant caustic taste when vaporized and inhaled, in contrast to the reportedly pleasant menthol flavor of PCP base. Formation of the HCl salts increases the palatability somewhat, although with PCE, there is still a distinctly unpleasant flavor (ref 14).

The N-ethyl derivative of PCP (PCE, evaluated for anesthetic potential as CI-400 by Parke Davis Co.) began to be seen in clandestine labs in the US in 1970, following which it was legally scheduled. Another similar analog that has appeared on the illicit market in the US is the N-propyl homolog (PCPr), which has not been scheduled. The compound with an N-isopropyl substituent appears to have similar potency to PCP, but the N,N-dimethyl derivative may be only 1/2 the potency of PCP. The N,N-diethyl compound has more active in animal models than the dimethyl analog, but still less than PCP.

An oxygen atom can be incorporated into the alkyl chain of the amino substituent to give a compound that retains activity. For instance, both the N-(2-methoxy-ethyl) and N-(3-methoxy-propyl) analogs are active in animal models (ref 11). The N-(2-hydroxy ethyl) analog has also been found on the street, and is presumably active.

https://www.erowid.org/archive/rhodium/chemistry/pcp/sar.html

Too bad about this:

Electron withdrawing groups seem to have a deactivating effect. A fluoro substituent or other halogen at the 3 position strongly reduces activity

 

[roi]

You should actually read the reference as well soli

http://pubs.acs.org/doi/abs/10.1021/jm00303a030

It only described 4-Fluoro-PCP, but not 3-Fluoro-PCP. The result is not very unexpected given 4-MeO-PCPs low potency as well.

 

[adder]

I wouldn't expect fluoro substituent to behave like methoxy there, the mechanism of potency decrease is unclear as well, if the ring needs to be fairly activated to interact with its site, then no matter where you put that fluoro, it's going to decrease potency unless it starts to do some magic at the meta position via electronic effects. Anyway, ketamine's overall potency is likely decreased by o-chloro if you look at MXE doses or 2-oxo-PCE (on the other hand they both bear N-ethyl), but qualitatively this substitution rewards any drop in potency.

 

[roi]

You could compare Ketamine with Deschloroketamine directly. Not only is the duration greatly increased, but also its potency (hole dose with no tolerance appears to be ~40mg). So yeah, 2-chloro substitution has a huge impact. On the other hand, 2-MeO-2-Deschloroketamine seems to be even less potent than Ketamine, isn't it?

2-Fluorodeschloroketamine however seems to be a tiny bit more potent than Ketamine, and also has a slightly longer duration.

Also 3-MeO-PCP seems to be a bit less potent than PCP, and 3-MeO-2'-Oxo-PCE a fair amount less potent than 2'-Oxo-PCE.

Guess we'll find out about the 3-substituted halogen in the next few weeks when some people have tried it. It's not impossible that it turns out to be quite potent.

 

[Solipsis]

It's not about 'whereverthehell' ring activation is it? The electronic configuration should behave somewhat similarly to the acid functions in the NMDA-like pharmacophore, assuming we are comparing rings that are all activated somehow (although clearly no substitution works well too)? Genuinely asking this, considering especially adder has a pretty awesome ACA resumé.

But yes I guess we will find out, I'm eager to see if this one and the TFM are potential for hypes, but will also kind of depend on the production not making these guys price themselves out of the market.

Damnit they messed up paraphrasing the reference? well spotted