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Knaus compounds

haribo1

Ex-Bluelighter
Joined
Nov 29, 2006
Messages
4,822
This series of VERY potent opioids are interesting for a number of reasons.

http://en.wikipedia.org/wiki/1-(4-Nitrophenylethyl)piperidylidene-2-(4-chlorophenyl)sulfonamide

The above compound is active at 0.0000037 mg/kg making it some 10000 times as morphine.

Two things interest me:

1-Substitution of the N pyridine is vital to activity. The patterns shown in the patent closely mirror those of the simple phenyl piperidine class of drug (demerol and it's reversed esters. The p-Nitro is the strongest of the demerol class (29x stonger than plain phenylethyl). Now compare the ratio in this class (the Knaus series). It's a 1000 times stronger.
2-The series also produces highly active antagonists. I suggest than further research could reveal some of the most potent antagonists known.

In Australia, they are pioneering the use of nalmefene implants which block opiates for a minimum of 6 months (nalmefene is 80x stronger than noloxone).
Imagine if we could produce an antagonist in the thousands times the activity. Implants could last for literally YEARS.

No duration is given for the series, can anybody guess the route of excretion? I'm non to familiar with the sulfonimine group....

Oh, one other technical question. Can the N-unsubstituted compound be produced allowing a large series of substituted phenyl-ethyl based groups. I seem to remember than the p-NO2 was the most potent, but the second best was introducing a double-bond. As far as I know, nobody has tried having BOTH variations in one compound.
 
The idea is a good one, but horrifies me at the same time. i am invisioning a future where a judge gives an drug offender the option of jail, or rehab that includes implants of this kind. Essentially I fear that these kind of implants could be forced on people, leaving them w/out options if they ever really require pain relief.
 
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