Contemplations on ketamine nalogues (bump)

[/navarone/]

This was my former post in the "draw random molecules" thread
____________________

Sup..
I wa looking for your opinion on 3 ketamine like substances that I came up with during my long and harsh methoxetamine intake.

Basically I was hoping for some lqualified info on the SAr and other potential properties of the following:

In my opinion the first 2 shold have a high activity, though im dubious abouth the third one.

Thanks in advance. anyways.

Peace!
_____________________

*Reply post was*

You're right. I'm not an expert, but the first two do look more active than the third. Third one looks a little.. eh. Not sure if any would match any of the current arylcyclohexylamines though. Really cool "triflu" section in the second one..

_____________________

*My response*

the 3' one actually fits prety well with metoxetamine on a 3D model though it this is only possible with one of the 2 isomers from what I undestood.

Could anyone advice me a better program than ACD to depict molecules and ther 'natural' comformation?
On ACD chemsketch the molecule seems plausible though i have doubts about that program a lot.

Neways here is what I managed to post in 3D so far to compare between methoxetamine, ketamines and my so called 'ponticlidine' (from italian 'ponte' which means bridge).

the general comformation of the molecules don't seem to alter that much so I would gues some activity....plus longer duration since the ethyl grouo is bonded between an amine an an oxygen making enzymatic brakedown moew difficult.

What do you think?
(ps sorry for the typos...im a lil bit drunk right now)

__________________ END

Now what would be your thoughts abouth these hypothetical ketamine analogue?
Also could someone advice me a better program than ACD to sketch out molecules and see their conformation?
Any remak will be apreciated.
Stay cool, stay safe, stay blue!

Ciao!

 

[ebola?]

Please try not to cross-post. I'll allow this, though, as the random molecule thread is too goofy for this.

ebola

 

[sekio]

I think you should read up on the SAR of NMDA antagonists and whatnot. Trifluketine is definitely a promising compound but as far as I am aware nitro groups are not exactly conducive for increasing the potency. Pontiketine is likely too sterically hindered to bind well.

 

[Odd_nonposter]

Disclaimer: I am, by no means, an expert on pharmacology.

I was under the impression that the blood-brain barrier screened out a lot of charged compounds. If that's the case, then nitroketine wouldn't have much activity.

The trifluoromethyl analogue of MXE might have some activity if the trend for activity depends on easily accessible nonpolar bulk at that region. I know that's the trend for phenethylamines.

 

[/navarone/]

Just think of many benzodiazepines. Nitro groups can cross the BBB.
The reason why I chosed the nitro group is for its ability to attract protons and form hydrogen bonding just like etheres (eg:MXE) do.

The problem with ponticlidine is to figure out at which aryl-rotational conformation binds to the receptor. The Images made by me are simply the least energy distressd conformation. However another carbon can be added to the 'bridge' to render a more flexible compound.

 

[mad_scientist]

3-bromo-PCP and 3-nitro-PCP are both inactive, so I'm not sure how successful your first two structures would be. The SAR of arylcyclohexylamines has been reported in quite some detail on this site if you search for it.

 

[/navarone/]

^^ Do you have any reference to that.
One more tng that went through my mind is that ethers are strong protons (H+) seducers and so is nitro AFAIK.
Also chloro and especially bromo are exellent for grignard substitutions.
One more cool thing would be converting the ketone to a bigger thioketone. The procedure doesn't seem that difficult on paper.

This is just a mindkerk though even if possible.