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I Like to Draw Pictures of Random Molecules

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14's a pretty magic spot for opioids. It sems like you just stick anything on there and it's a winner. Case in point; 14-PPOM.
 
That sweet spot oxygen on those morphinans, has it ever been just given a nitrogen? or a sulfur with crazy direct attachments.

My thought as morphine family goes is 6-(every hard pressed ether) 3-(every rapidly cleaved ester) in a cocktail with the top twelve or so HCl or perhaps even protonated differingly a la Adderall's 4 salts. Somehow I think that would be warmer, quaint, and more natural (well, spans it wider) than some other semi-synthetics. 3-(easily cleaved and more solute) 6-(hard to cleave without blocking coupling) morphine. Call it maybe multilaudiphine after laudinum
 
Nagelfar said:
That sweet spot oxygen on those morphinans, has it ever been just given a nitrogen? or a sulfur with crazy direct attachments.
Click to expand...

There are compounds like beta-naltrexamine, with an amino nitrogen on 6-carbon, and nalfurafine with amide nitrogen there, but they are usually not agonists at mu receptor (they're either mu blockers, kappa agonists or both).

www.eurekaselect.com

Functionalization of the Carbonyl Group in Position 6 of Morphinan-6-ones. Development of Novel 6-Amino and 6-Guanidino Substituted 14-Alkoxymorphinans

The well-known opioid agonists, oxycodone and oxymorphone, and the opioid antagonists, naloxone and naltrexone, are commonly used clinical agents and research tools in the opioid field. They belong to the class of morphinan-6-ones, and produce their pharmacological effects by interacting with...
www.eurekaselect.com

Then there's the strange compound N-naphthoyl-β-naltrexamine, which targets mu-kappa receptor dimers without having much of the side effects of either mu or kappa agonists (but seems to produce some place aversion at high doses).

And if you meant a 14-amino substituent, then there are these 14-cinnamoylamino compounds, some of which are buprenorphine-like partial agonists: https://link.springer.com/chapter/10.1007/128_2010_89

Maybe there's some easier way to get a 14-hydroxy on codeine than full conversion to oxycodone... Then it would be easy to make those phenylalkanoate esters Sekio posted about.
 
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Yes I meant 14, the 6 position was my addition since I can't find a chemical drawing prog. for my phone
 
Do that cinnimate 14 to acetorphne see what happens, that, or nearest in synth., is my imaginary pic contribution: edit the pesky endoetheno bridge by inverting the ring one space removed, (up one side, down other) but who knows what that'd do. New biomimetic synth of morphine anyone?
 
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The cinnamic acid ester of oxycodeinone
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I suspect that it's actually oxycodone cinnamate, i.e. the double bond is reduced.... the same paper that details the other 14-esters has 14-cinnamate as 175 +/- 75 x morphine potency (oxycodone itself at 0.3x).

I was under the impression that codeinone and 14-hydroxycodeinone are crap analgesics.
 
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Nagelfar said:
Do that cinnimate 14 to acetorphne see what happens, that, or nearest in synth., is my imaginary pic contribution: edit the pesky endoetheno bridge by inverting the ring one space removed, (up one side, down other) but who knows what that'd do. New biomimetic synth of morphine anyone?
Click to expand...

Came to the library (shift + PrtScn-SysRq & ctrl v have been the same since the '90s, yay for me. Getting old)


sekio-Acetor-And.png


(Edit: change above by putting the bottom bridge end to the seven position where the alcohol is, so it's symmetrical)

And because I can't resist the speedball:

cocainolog.png
 
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sekio said:
I suspect that it's actually oxycodone cinnamate, i.e. the double bond is reduced.... the same paper that details the other 14-esters has 14-cinnamate as 175 +/- 75 x morphine potency (oxycodone itself at 0.3x).

I was under the impression that codeinone and 14-hydroxycodeinone are crap analgesics.
Click to expand...

You can even make that cinnamoyl ester from naltrexone and it will be a weak mu partial agonist. The 3-methylated codeine-like version of that has more of agonist effect:

 
I just did a search and found a 1992 findings article on pethidine derivatives made with a tropane substitution, I can't figure how to copy words and addresses with my phone so if someone has access to the article (top of Google search nearly for me) would someone so willing post one or two here for me?

The words "pethidine", "opioid" and "tropane" seem to work

Also: if you go to molview.org and type in Anthraxiton you get a strange compound. WP has no such entry. Could somebody identify it?
 
Anthraxiton is brand name for sodium salt of diclofenac which is shown
 
Nagelfar said:
I just did a search and found a 1992 findings article on pethidine derivatives made with a tropane substitution, I can't figure how to copy words and addresses with my phone so if someone has access to the article (top of Google search nearly for me) would someone so willing post one or two here for me?

The words "pethidine", "opioid" and "tropane" seem to work
Click to expand...
I believe this is the article you are referring to.
 
Double-DATAllosteric.png


Above the synthesis of both those allosteric modulators at DAT in my recent threads nobody has responded to yet. ; -P

Double-DATAllosteric2.png



compound 11a (PMID: 23022052 Click here)
+
compound SoRI-20041 (PMID: 19244097 Click here)

I made sure to overlay with how the tropanyl in the one would match the benztropanes analogy in the other. Viable as *anything* that can be said for QSAR having theoretical probability (which I believe is null in most cases, but certainly not in divergent drugs spliced into one portmanteau)
 
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That has a Texas carbon. Not sure how stable a hydroxy/amidine (apparently a carbamimidic acid? thanks chemdraw) would be either?
UdEzP5I.png
 
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sekio said:
That has a Texas carbon.
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The middle arene beside the penta-spiro and opposite other aryl? That what it's called? Yeah just now wishing I could rotate the faux pi-symmetry cake walk / Chinese firedrill style one carbon around.

Oh yes the fifth link on the spiro, I just thought it'd look cleaner but yeah it's still be five. At least Texas, as you say, is between the hydroxy and the nitrogens then ; -j : -P
 
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I would think that the compound with the "right" structure would rearrange to a N-hydroxy-amide...
n8QpkZM.png
 
All cyclopentanes or just the above? Other ones from the paper, such as the one that works on SERT may be more viable? And if you mean my verbal correction of it I was already beginning to think I was right the first time around.
 
Just another thought about the 3-methyl-14-cinnamoyl-naltrexone: if this is almost a full mu agonist, and the 3-demethylated metabolite is almost a full antagonist, it could possibly cause some kind of 'hangover' even after single dose because the activation of mu receptors is suddenly replaced with blockage of them.

And start redosing at that point and you're soon in real trouble...
 
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