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Interesting Ketobemidone Analog

haribo1

haribo1

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US Patent 3,043,844 discloses an analog of ketobemidone which is minus the meta -OH but rather than N-methyl, has a phenyl propenyl. It's described as 'an analgesic and antitussive' but no specific measures of potency are given. Has anyone got a Merck to check this out? With the pethidine esters, the phenyl propenyl is 29x more potent but ketobemidone without the meta -OH shows minimal activity. Since this is potentially a legal (in the UK at least) analog, it holds a deal of interest to me.

Thanks in advance,
H-)

PS Any information on other ketobemidone analogs would also be greatly appreciated.
 
Not that I particularly want to get involved with this but apart from the obvious legality of a compound there is also the synthetic route which one has to think about.

If it requires a controlled drug or controlled precursor in order to make it - it's as good as controlled itself.

As for the chemistry itself I wouldn't know and also it's against the rules to discuss specific synthetic routes but just thought I would add my 2 cents.
 
Oh, the synthesis is quite trivial but I've simply never seen a phenyl piperidine with an ketone in this class. OK, methadone and the like, but all this class have a meta hydroxy. I'm not interested in making it (though I would like to know the potency) but rather I enjoy punching holes in MoDA, just for fun. This is strictly mind chemistry...
 
haribo1 said:
Oh, the synthesis is quite trivial but I've simply never seen a phenyl piperidine with an ketone in this class. OK, methadone and the like, but all this class have a meta hydroxy. I'm not interested in making it (though I would like to know the potency) but rather I enjoy punching holes in MoDA, just for fun. This is strictly mind chemistry...
Click to expand...

the trouble with punching holes in the MoDA and publicising it, is that it will encourage the puritanical simpletons who write the law to create a vague woolly analogue law along the lines of their laws on terrorism where doing anything, having anything, thinking anything can be a crime subject to the whims and vagaries of the legal system.
just a thought.
 
The particular analog you are referring to is 4.5 times more potent than pethidine (in rats or mice i presume).

This is from the book "Drugs affecting the central nervous system" in the chapter on morphinelike analgesics, written by no other than Paul A. J. Janssen himself.
 
Wow, Mr. Janssen himself! I really must get that book for christmas... I don't suppose an analogue with a meta-hydroxy on the ring (as in ketobemidone) was also tested? Keto analogs without it seem low-powered, the same N substitution on pethidine or reversed esters showed a potency x29 the patent compound so that's an awfully large drop-offf. Oh, and anything on the 3 position on the piperidine ring...

Thanks for the reply.

Oh, meta-OH AND 3 alkyl DON'T work AFAIK...
 
Oh, here IS that list of pethidine analoges (change the N-methyl too)

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Oh, one last thing, apparently Ketobemidone is an NMDA antagonist (like methadone, PCP & Ketamine) so it has a dual method of pain control. I wonder if these analogs posess such functionality & to what extent they enhance the analgesic effect. All I know is that too many NMDA antagonists makes for an awful withdrawal....
 
haribo1 said:
I don't suppose an analogue with a meta-hydroxy on the ring (as in ketobemidone) was also tested?
Click to expand...


No, sorry. But they do give data for the methyl ketone and propyl ketone analogs of ketobemidone however. (Methylketobemidone and propylketobemidone they are named on wikipedia.)

methyl - 3x pethidine
propyl - 2.5x
ketobemidone - 8x
 
So, that confirms the ideal leangth for the ketone part of the skeleton. I don't know why, but the potency compared with the simplicity of the ketobemidone system is something I find very interesting. I mean, sure, certain ohmefentanyl analogs may well be 16000x morphine, but I don't see them being produced and of course they are already illegal.

Now, that meta-OH increases pethidines potency (making bemidone) as well as ketobemidone (without the meta-OH it's potency is 0.7x pethidine) BUT I fear that the N-methyl size may well stop that increase being so pronounced. Pity really, since ketobemidone is x8 pethidine and the phenyl propenyl analog of pethidine is x29, if those two multiplied together you would combine reasonable simplicity with quite high potency (and thus punch a neat hole through MoDA... which is always fun ;-)
 
I have now found the information that you crave. But you will not like it... N-cinnamylnorketobemidone is only 0.9 times pethidine in potency. I found it in the book Analgetics by deStevens (1965).

I will quote a small section:
The N-cinnamyl analog (No. 5) shows reduced activity compared to the parent compound, ketobemidone, just the opposite of the markedly improved activity of N-cinnamyl analogs in the meperidine series. N-cinnamylnorketobemidone is about equal to meperidine in potency (Eddy hot-plate), does not support physical dependence in monkeys, and is not an antagonist. This is another example of an unusual combination of good analgetic properties without serious side effects, if this compound is truly a potent analgetic rather than a general central nervous system depressant.
Click to expand...

The N-(3-phenylpropyl) is also mentioned and is about the same in potency.

The reference they give is for an obscure journal, Bull. Drug Addiction and Narcotics, No 24, Addendum 2 (1962). Would be interesting to read, but I can only find one library that has it, and it's on another continent. http://www.worldcat.org/oclc/46403690?sloc=New+York
 
Does anyone know the receptor profile agonized by the methyl analogue of (ethyl)ketobemidone? I imagine it would be very similar, no?
 
ralf2 said:
No, sorry. But they do give data for the methyl ketone and propyl ketone analogs of ketobemidone however. (Methylketobemidone and propylketobemidone they are named on wikipedia.)

methyl - 3x pethidine
propyl - 2.5x
ketobemidone - 8x
Click to expand...

Is there any info available on the iso-propyl one?
 
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