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Benzimidazole opioids (Isonitazene and related) placed Schedule I by DEA..

tWCBSwh.png


NowI friend actually asked Dr. Danial Lednicer of the p-Me analogues of BDPC (and related) were as potent BDPC. His papers showed the p-Me & p-Br to be equally potent (by mole) i.e. some x40 their parent. His answer was simple 'we were so lauded after BDPC tuned out to be so active we team simply didn't have the time to check. Now for what it's which, I think that the p-Me and I would expect that p-Me to be oxidized and removed from brain tissue. I also suspect that N-dememthylation is the route by which BNPC is removed from the body.

Adding a sacrificial moiety that is also important for the action of the drug looks elegant. I've wonder if anyone has tried the 2-furyl homologue.
I have never tried any of the BDPC analogues but from what I have read, it's great for 4 hours, not so great for the next 8 hours. I suspect that N-demethylation is the cause. since such metabolites are kappa & delta selective.

 
@clubcard : ^ MOR agonist, partial agonist or antagonist?? afaik Pfizer ppl never disclose that (functional assay) for those compounds. only they're potent ligands! but so is naloxone!
 
So I have a question - if the amine of the above drug was a tertiary, would it exert most mu activity? I'm not saying it does, but I notice many similar actions. The 6-methylenes between the aromatics and so on.

AFAIK we dimply did not have a sufficient number of highly active mu logands to build a training set. My feeling is that we still need more.Etorphine is interesting.
 
clubcard said:
tWCBSwh.png


NowI friend actually asked Dr. Danial Lednicer of the p-Me analogues of BDPC (and related) were as potent BDPC. His papers showed the p-Me & p-Br to be equally potent (by mole) i.e. some x40 their parent. His answer was simple 'we were so lauded after BDPC tuned out to be so active we team simply didn't have the time to check. Now for what it's which, I think that the p-Me and I would expect that p-Me to be oxidized and removed from brain tissue. I also suspect that N-dememthylation is the route by which BNPC is removed from the body.

Adding a sacrificial moiety that is also important for the action of the drug looks elegant. I've wonder if anyone has tried the 2-furyl homologue.
I have never tried any of the BDPC analogues but from what I have read, it's great for 4 hours, not so great for the next 8 hours. I suspect that N-demethylation is the cause. since such metabolites are kappa & delta selective.

Click to expand...
 
If nothing else, you have a ligant x10 etonitazene but the BDPC analogue is potent and if someone were prepared to simple 3D QSAR the compounds, light may dawn. Dezocine is active and has a primary amine. It isn't the N itself, it's the N: that is important. The same is true on the ⭕ and :S: atoms seen in certain other opioids.
 
Oh I'd love to see some BDPC relative again on the market. That stuff was awesome even when, from a harm reduction perspective, I don't like the potency of it at all and think such potent opioids in the greedy hands of capitalists are a disaster waiting to happen.

Do you have any idea for a balanced mu-delta agonist and kappa antagonist, possibly with some NMDA antagonism?
 
dopamimetic said:
Oh I'd love to see some BDPC relative again on the market. That stuff was awesome even when, from a harm reduction perspective, I don't like the potency of it at all and think such potent opioids in the greedy hands of capitalists are a disaster waiting to happen.

Do you have any idea for a balanced mu-delta agonist and kappa antagonist, possibly with some NMDA antagonism?
Click to expand...

It turned up. Reports stated that thefirst 4 hours were good, the following 8 hours not sogood. Well, it seems to me that N-demethylation is the only metabolic route for BDPC BUT swapping the -Br for a -CH3 (check the papers) and the compound is just as potent but the duration is only 2-3 hours because that p-Me provides the body with a convenient place to oxidize.

I would be surprised if other aromatics (other than phenyl & 2-thiophene) would be active. In the fentanyl class, 2-furyl was active

In short, this looks like another practical route for a high potency opioid.

I might add that I think high-potency with a short ½ end up being sold on the street like crack. I've seen $5 of fentanyl because with a duration of 20 minutes, people want MORE and FAST so the low-cost many unit model ensures that MANY units are sold. Of course,some compounds not even in the DOI lists are active (some very).
 
6-methoxy-1-(2-diethylaminoethyl)-2-(4-methoxybenzyl)benzimidazole.png


ELENA
6-methoxy-1-(2-diethylaminoethyl)-2-(4-methoxybenzyl)benzimidazole
 


I do apologize for poor quality but once again, a methyl moiety seems important for potency.
 
The problem is - people die. Now I can argue that they had pure material and they should have known better but my brain does not work like that. When I discovered that an ex-H addict had been given 250mg of U-47700 I was not happy. That he died several days later makes ME feel responsible. I asked for 2mg soluble tablets but the makers just wanted $$$ which is why I have avoided them. I didn't know the guy but his GF was in bits, I dare anyone to try the 'he knew the risks' line for someone is grieving.

I posted this just to make it clear that we WILL sooner rather than later provide substitution therapy.

I WAS interested by the QSAR but to be honest, the people who could work this out can work out their own meds. For me, INT (isonortilidine) is the best. 2 step synthesis, opioid action same as M, speed action the same as dexamphetamine, NMDA action like K....
 
Well the 'Morphine Rule' states:

-Aromatic system
-Quaternary amine
-2 carbon chain
-tertiary amine

Now it isn;t REALLY a rule but you will find 90% of opioids fit.

With etonitezine,MANY analogues were made and weren't active so if you hit the papers, you will soon sort out the nonsense.
 
clubcard said:
So I have a question - if the amine of the above drug was a tertiary, would it exert most mu activity? I'm not saying it does, but I notice many similar actions...
Click to expand...
who knows? It would certainly increase logP and desolvation energy that may or may not contribute to increase Ki. one never knows what to expect with a methyl! its called "magic methyl" for a reason in the trade. either it improves dramatically or kill activity altogether, or go from agonist to antagonist or the other way around.. but who knows?

Ethazocine.png

Ethazocine
I still believe, anazocine (or related) is probably as close as its gets to morphine in terms of overall profile. fent are shit , just killing ppl and not even euphoric . now this compound is ~10xM . macaque monkeys will glady prefer it to morphine!!! pretty straigthforward 2-step synthesis from dirt cheap promegranate tree alkaloid pseudopelletierine. Notice how it is not chiral so probably may have some NMDAr antagonism too..
 
In the case of opioids, it's the position & direction of the N: ion. Work was carried out using morphine methyl bromide (so 2 isomers) and only 1 was active in the in vitro testing. If you look at the N: in nortilidine & the N: in desocine, you will note that their is a distinct pattern.

Now I have mentioned that a phenolic -OH can be replaced by a -CONH2.

Sadly I do not have a large enough training set to find out why allylprodine, 14-Cinnamoyloxycodeinone,and related rareand unusual compounds are so active. Oh, I forgot another high-affinity scaffold.



This metofoline analogue that was x168 morphine based on Straub tail test results and x94 in the tail withdrawal test.


I have always been interested in this class. I suspect that the S=O is a bioisostere of the C=O derivatives of phenoperidine and other related compounds. I would argue that since this compound doesn't even turn up in Reaxys, anyone could ask the Chinese to make it because unless they have a member of staff who read '1975 Annual Report in Medicinal Chemistry' (unlikely), chances are they would have no idea what they were making, But of course, I do not know how commercial the precursors are.

As a rule of thumb:

1 step - still requires preparation and workup but available to Chinese developers
2 step - Extraction of product needs to be ensured because GIGO and while the Chinese will make it, they will not see it as an easy ride. Also, have 3rd party GC-MS & NMR carried out. The Chinese WILL send the instrumentation of their bench-scale product, not the stuff made at scale
3 step - Products become 'dirty'. I have said it so many times but I have seen instrumentation results that were TERRIBLE. I mean dimers, trimers and impurities. While the pure compound may vapourize, the dimers and polymers will not and synthetic CB ligands have Ns in their structure. I expect a spike in lung cancers due to this crap.
4 step - get a European 'fine chemical' manufacturer to do the job. Yes, you WILL pay more, but the results are so clean. While $20000/kg seems like a lot, that made 2 million pyrazolam tablets that sold for 50p - £1 each.

Now the Chinese are cost conscious to the extent that they wouldn't even clean the G-130 we had made because acetone 'is controlled'... like I'm an idiot. So I told the boss I would clean it and we pay for the pure material..... well 14% were side-products. If you want complex done well, do not trust Chinese.

I should add that I have liked all of the Chinese people I have met but they do have a common business saying saying '如果可以作弊，那就作弊。' - 'If you can cheat, cheat'. so we dumped ALL of our Chinese suppliers and used EU labs. Products was consistently fine.
 
Yes, but the EU labs that I've seen won't ship to the United States.
 


Now the ethanesulfonate moiety has the unusual property of being a bioisostere for an ester, reversed ester of ketone. It is tolerant of a m-OH (or m-C(O)NH2 - a bioisostere of a phenol)

I do not think anyone has tried adding 3-hydroxy-3-phenyl propane moiety to A or if ring-substitution has been tried on the piperidine ring but it's a heck of a precursor. AFAIK if A is a H, the compound is inactive and thus legal everywhere. It simply means that for every phenylpiperidine opioid - the number of possible isomers just doubled.

The propylsulfonate is just as active BUT turns out to be more toxic (lower LD50). All I am trying to do is to place a sufficient number of novel, potent opioids into the hands of as many people as possible.. Just in passing, their is a damned great hole in the MoDA CC methylorivnol. The compound itself is some x40 M in potency. The reason it's of value is that during the synthesis of etorphine or related, the methylorivnol has to be purified & protected for the grignard so it's generally a batch process so people who do not officially sell the stuff WILL have it if they make Bentley Compounds .

Interesting that in 7-PET, a 2-phenylethyl is a biostere for an N-pentyl. Close observers will also noted that pyrophenidone uses a phenyl ring to substitute for the N-pentyl of pyrovalerone. That's a BIG area, bioisosteres.
 
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This is a case where those of us blessed with autostereogram are onto a winner because even though it does not seem similar to fentanyl, in fact they overlay quite well.
 
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