N&PD Moderators: Skorpio
A fentanyl analog without NaBH4
haribo1
Ex-Bluelighter
One of the steps in the making if MOST fentanyl class drugs is the formation & reduction of an imine using NaBH4, I noticed in the synthesis of carfentanil that the imine is reduced & a -CN plonked onto the 4 position of the piperidine ring. Now, I strongly suspect that it will not be toxic & 4 methyl fentanyl is stronger than plain fentanyl. So, any ideas on 4-cyano fentanyl?
mad_scientist
Bluelighter
The pethidine analogues with CN in place of COOEt are active, so I'd say 4-CN-fentanyl probably would be too.
Substitution on the 4-position of fentanyl is quite an interesting area, seeing as 4-methyl, 4-phenyl and 4-COOCH3 derivatives are all known to be active it suggests that a fairly wide range of substituents would be tolerated, I'd be interested to see what else might work.
mad_scientist
Bluelighter
Not all nitriles are toxic, once the molecule its attached to gets over a certain size then the CN group has too much steric hindrance to bind to cytochrome c oxidase and disrupt the electron transport chain (hence no "cyanide" type toxicity)
Its not a very commonly used substituent in pharmaceuticals, but there are some common drugs with nitrile groups in, citalopram is the most obvious example that comes to mind.
mad_scientist said:
This sounds like utter nonsense to me. Care to provide a source?
things like acetonitrile aren't toxic as is due to the cyanide group being a poor nucleophile while attached to an R group.
The toxic effects of all cyano groups are due to the cyanide ion (or a nitrile with a weak bond) being liberated.
You look at the LD50 of rodent APAP or NaCN... about the same
EDIT: acetonitrile and APAP; not NaCN and APAP
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hugo24
Bluelighter
Be aware that Acetonitrile IS quite toxic,it is often underestimated.One case I know had a bottle broken on the floor and because he didn't strip off contaminated shoes and socks he developed toxic signs/cyanosis several hours later (at home) becoming an emergency case for the hospital.Yeah he survived but the case was made public to inform people about the real dangers of AcN.
You're right nitriles are toxic because of liberating cyanide.
hugo24 said:
1. As I said acetonitrile isn't very toxic compared to other things we work with, consume, and it itself isn't toxic at all absent metabolism;
2. The only real danger w/ aceonitirile is its relativly low boiling point and the fact that it is a liquid. Therefore you have both transdermal and inhalation risks w/ it that you don't encounter w/ most things. If tylenol had similar properties, and we worked w/ liter quantities of that, you'd have the same problems.
Ham-milton
Bluelighter
I really loved diphenoxylate. It's underestimated as an opioid. Probably because of the tropanes the products are stuffed with (I can't recall which one. atropine?)
Ham-milton said:
If you'd be willing to describe this more, I'd appreciate it.
Was it qualititativly like other opioids, morphine, hydrocodone, oxycodone? Did you encounter the atropine side effects at all?
Any info would be appreciated, thanks!
Ham-milton
Bluelighter
I thought it felt similar to pethidine. Not so much like hydro or oxy, but then again, not that far removed, either.
It was just a mellow, itchy goodness. No over-the-top euphoria like Heroin always give me. I didn't use it a lot either, though
I went pretty high with the dose, actually, and I actually didn't notice anything from the atropine that was problematic. My mouth was drier than it should have been, and my pupils were dilated, both of which I assume were from the atropine.
Acyl
Bluelighter
"Diphenoxylate is approximately one order of magnitude more potent as an antidiarrheal agent than morphine. 'Diarrhea level doses' of diphenoxylate show little of the other morphine like actions. However, in doses approximately 25 times the antidiarrheal dose, diphenoxylate is a typical opioid with all that this connotes."
Ham-milton, did you extract the substance from the atropine pills? What was your dose?
haribo1
Ex-Bluelighter
Having got over the fact that the nitrile isn't deadly poison, has anyone got any research on the 4 cyano fentanyls potency? Aniline + piperidone + KCN yields the substituted NPP so you just add propanoic anhydride. Granted, getting propanoic anhydride isn't easy, but sodium propanoate is used as preservative in bread. Easy to get the free acid & simple to make the acid chloride or the anhydride...
fastandbulbous
Bluelight Crew
Another 'too much synthesis' talk in this thread. It's getting close to euthanasia
MattPsy
Bluelighter
Acyl: I've tried diphenoxylate recreationally up to a dose of 37.5mg. I quite enjoy it, but the motillity issue is just torturous.
http://www.bluelight.ru/vb/showthread.php?p=5126803#post5126803
^ That's just 25mg though. The 37.5mg lasted for about 10 hours peak, then a slow return to baseline. Was blissed out relaxation with lots of euphoria when cigarettes were smoked.
So, I guess that CN group is okay.
fritzy
Bluelighter
haribo1 said:
IIRC, there are a number of reports of exactly these things being synthesized in the open literature. A quick substructure search using SciFinder or Beilstein Crossfire would come up with a nice summary of what's available; I trust you already have managed to learn to use these tools, and if you haven't you really should.
LuxEtVeritas
Bluelighter
^ ...and even if ya did ....
