Pharmacology Opioids - 3 aromatic rings (or at least fragment of a third)

[AlsoTapered]

Anybody else noted that norbezitramide has 3 benzene rings and is x20M. Allylprodine has a fragment (an allyl) of a second aromatic and is x4 prodine and crazy things like R-4066 (a methadone derivative) is x212 M? Or 4-phenyl fentanyl x6400 M.

I kept saying that nobody had listed all the key moieties,

1-benzene ring (a)
2-benzene ring (or fragment) (b) 2-3 methylenes from 2
3-aromatic ring 6-7 methylenes from (a)
4-Positively ionizable function
5-hydrogen-bonr donor
6-hydrogen-bond acceptor

There are also small side-chains (like in 3-methyl fentanyl/prodine) that are not fully understood but most papers guess 'increase molecular recognition. In fact, they just allow the compound to lose more energy as they bind to receptor i.e. increases affinity,

So not there quite yet... but getting closer every time.

 

[MedicinalUser247]

Well you got your work cut out for you there because there's over 1400 fentanyl analogs know to exist over all.

 

[AlsoTapered]

Well you got your work cut out for you there because there's over 1400 fentanyl analogs know to exist over all.

You seem to have failed to understand the point being made I gave examples of a number of classes that contain all 3 aromatics and as I pointed out, compared to the analogues lacking them, they are much more potent.

When I mention 'fragment' I mean an allyllic group because like an aromatic group, they have pi bonding (p-orbital that is conjugated with the adjacent pi bond).

By all means question - but if you don't understand the original statement, don't presume to correct people. Believe it or not, you are NOT an organic chemist and much less a medicinal chemist. I have always tried to fairly and reasonably correct your mistakes and to explain misunderstandings. For a start, you should have looked at all the compounds I named to see the commonality.

Your statement just underlines the fact you should be making at least SOME effort yourself. Note that 32 other people also read the thread and none of them felt justified in correcting me. It's not like I'm the most qualified person here, but I did study the subject for 8 years formally and informally.... 27 years.

 

[MedicinalUser247]

As far as I know carfentanil or (4-methoxycarbonyl)fentanyl is the strongest opioid known so far. A lot of opioids are related to morphine which have the features your talking about which include 3 rings, 5 rings and 6 hydroxyl groups, alcoholic and phenolic, an a piperidine ring that has a N-methly group an a quaternary carbon at position 13. Morphine can be modified in many ways. Fentanyl can be modified much more. That's why I stated that there are over 1400 analogs. If you wanted to create something stronger or more euphoric instead there are many ways to do that. It all comes down to your own hypothesis. I didn't mean to offend you in any way and I have the utmost respect for you.

 

[AlsoTapered]

As far as I know carfentanil or (4-methoxycarbonyl)fentanyl is the strongest opioid known so far. A lot of opioids are related to morphine which have the features your talking about which include 3 rings, 5 rings and 6 hydroxyl groups, alcoholic and phenolic, an a piperidine ring that has a N-methly group an a quaternary carbon at position 13. Morphine can be modified in many ways. Fentanyl can be modified much more. That's why I stated that there are over 1400 analogs. If you wanted to create something stronger or more euphoric instead there are many ways to do that. It all comes down to your own hypothesis. I didn't mean to offend you in any way and I have the utmost respect for you.

Yes - because they contain some of the OTHER key moieties I pointed out. If you didn't know their meaning, you could have SO EASILY Googled them. You see - I PRESUME people have some knowledge or they will realize they don't have the knowledge and make the effort to acquire it. R-30490 is listed as the most potent fentanyl analogue BUT nobody had made the beta-hydroxy derivative (which would have the hydrogen-bond donor), for example, but when you get to roughly >x1000, how potent the opioid is in vitro varies from person to person. Nobody can say it's x 300000 M because the effect will vary HUGELY between individuals.

Please, learn some medicinal chemistry. If it was a valid point and I had made a mistake I WOULD like to know. But to be wrong and then & after correction, continue down the same path, ignoring the response is just lazy.

It won't be a problem for me - do it again and I will simply block you. You can't teach someone who BELIEVES they know better so it would be a waste of both our times.

 

[Skorpio]

Hey @AlsoTapered, can you be a little nicer about this stuff? People here have all kinds of different backgrounds regarding medicinal chemistry, and chastising people for not upholding your standards is counterproductive. Let people learn to like chemistry rather than chasing them away, innit.

 

[AlsoTapered]

Hey @AlsoTapered, can you be a little nicer about this stuff? People here have all kinds of different backgrounds regarding medicinal chemistry, and chastising people for not upholding your standards is counterproductive. Let people learn to like chemistry rather than chasing them away, innit.

I'm free to block whomever I choose am I not. My first response was MUCH milder because the person had clearly missed the point.... and then they compound the error because they apparently didn't look at the compounds I suggested and plowed on STILL failing to grasp the point.

On other threads I have gone to a lot of time and trouble to REALLY explain the QSAR and yet it seems that I put in the effort, they don't. So it's not like I snapped after 1 post - I spent about 3 hours providing them with information (all checked and reffed) and didn't even get a thank you.

So yes, maybe I am being snappish - but you cannot teach someone who doesn't want to learn. It's a waste of time for both parties. I'm not angry, just a bit annoyed that I put in so much effort for someone who doesn't want to learn.

Sorry.