• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Ketone analog of phenoperidine

haribo1

haribo1

Ex-Bluelighter
Joined
Nov 29, 2006
Messages
4,822
In the UK, the pethidine (demerol) type analgesics and the reversed esters are illegal by virtue of an analog law. BUT, the ketones (except ketobemidone) are not controlled. So, following this logic, would the keto analog of phenoperidone would therefore be legal in the UK....8)

ca1_3_18.png


Oh yes, I also notice from the patent for carfentanil that the aniline & substituted piperidone when mixed with CN form the ANPP directly, no imine to reduce. WIth this in mind, one could produce quite a simple synthesis.
 
Last edited:
Interesting just don't forget what happened with MPTP...

http://en.wikipedia.org/wiki/MPTP

Potentially risky avenue to explore surely? Fairly similar structure. Horrible outcome from MPTP (although good for parkinsons research)
 
Last edited:
Reminisant B said:
Interesting just don't forget what happened with MPTP...

http://en.wikipedia.org/wiki/MPTP

Potentially risky avenue to explore surely? Fairly similar structure. Horrible outcome from MPTP (although good for parkinsons research)
Click to expand...

The structural requirements for MPTP-type neurotoxicity seem to be quite specific though, as a lot of compounds that are structurally similar don't cause the neurotoxicity.

On the other hand I agree that it is pretty risky with new compounds of that family as there doesn't seem to be any reliable way of predicting whether they will be neurotoxic until they have been made and tested!
 
MPTP comes from a reversed ester being dehydrated. Making the Ketone from -CN + grignard shouldn't lead to such problems.
 
while we're on the subject, does anyone know the enzymatic/chemical mechanism by which mptp causes it's toxicity? I can see that double bond irreversibly binding to some transporter/enzyme that is vital.
 
kidamnesiac said:
while we're on the subject, does anyone know the enzymatic/chemical mechanism by which mptp causes it's toxicity? I can see that double bond irreversibly binding to some transporter/enzyme that is vital.
Click to expand...

I am not totally certain as there are a few things that don't fit the picture, but essentially it oxidises to MPP+ with MAO B, and then MPP+ does a few things, it causes VMAT 2 to dump dopamine into the cytoplasm which is linked to oxidative stress, it also can generate free radicals itself and seems to effect the mitochondria of the dopaminergic neurons. because MPP+ is permanently charged it cannot get back out of the cell. I suppose that MPP+ is quite close to NAD and NADPH energy carriers.
the double bond enables the oxidation to the charged aromatic species to occur easily whilst the tetrahydro compound is lipophillic enough to get into the brain.
an interesting prodrug to a neurotoxin.
 
I don't quite see how it goes from the diene to the pyridinium, but i suppose someone has it worked out...
I also think that doesn't bode well for the long-term exposure=parkinsons theory, as eventually the cell would apoptose and the mpp+ would not go into other cells (or would it?), so single oxidatively damaging events shouldn't cause parkinsons onset and symptoms, IMO. but I don't know a lot about the disease.
sorry to hijack your thread :)
 
You must log in or register to reply here.
Top