Fertile
Bluelighter
- Joined
- Mar 31, 2022
- Messages
- 1,627
US Patent 3278382A
'2-amino-5-aryloxazoline compositions and methods of using same'
Example XVIII
So just for the record, MDAR was first synthesized and tested in 1962. It's not a particularly demanding target BUT it is SLIGHTLY more difficult than rubbish like p,4-dimethylaminorex (DMAR). I've mentioned this before but Dr. Dave was VERY clear that 4-methyl aminorex is an MAOI while aminorex is not. Unlike 4-MAR it does not have a trans-cis pair, simply (R) & (S) stereoisomers.
I'm just going through and providing people with firm reference for all of the facts that I have asserted. Synthesis discussion is not allowed but I think it's OK to say that we tried several routes and the Henry Reaction proved to be the best. Cyclization needs nasty things. Do not try this at home. I just forgot where the reference was until I used the appropriate search engine.
What is it like? Well I didn't taste it, but the reports suggest that it's an entactogen with a dose range similar to MDA. This makes sense, but in medicinal chemistry, their are often totally unexpected results when a ligand is even slightly modified. We refer to this as 'the magic methyl effect'. I remember one report which stated 'this is the greatest drug legal or illegal I have ever enjoyed'. A rare ++++ event.
We also tested 4-methylaminorex (PAR) & 3-methylaminorex (MAR). The former is almost exclusively active on SERT and is very subtle until very high doses are consumed. The latter appeared to be DAT>NET>>SERT. A 2:1 mixture of the 2 positional isomers produced effects almost identical to those produced by MDAR (based on reports who tried them all). I DID sample those 2 individually, as a 1:1 mixture and finally as a 2:1 mixture. We didn't like the fact that it required 2 compounds (twice as much potential for unexpected toxicity) and thus we pressed on to MDAR.
Aminorex has 5HT2b affinity so regular (daily) use can cause heart valve damage in just 28 days. It seemed that 5% of people suffered this fate but the other 95% showed no change in cardiac function whatsoever. We figured that people do not tend to take entactogens daily or multiple times a day, unlike stimulants.
I include a very good article on the 3D QSAR of aminorex derivatives:
www.ncbi.nlm.nih.gov
Note how many chemists looked at the p-F homologue and thought 'wow - I can profit 4 times as much!!!' but the truth is, PFAR lasts too long for most people. We specifically went for the plain methyls because they act both to make the ligands selective but also serve as sacrificial moieties (groups designed to provide the body with a metabolic pathway not limited to a specific CYP liver enzyme). So their duration is about the same as MDMA/MDA.
Can one ring-substitute to provide significant 5HT2a affinity? Well oddly 2CB-Aminorex did turn up in Sweden in 2018. But reports suggest that it might have stimulant effects, but that is all. I think sekio suggested it was an internal standard although I note that someone tried adding the 2,5-dimethoxy-4-bromo moieties to just about every class of stimulant known. I mean, they did it to benzylpiperazine... That seems just reckless to me. What if it had proved to invoke irreversible 5HT2b binding (just an example)?
'2-amino-5-aryloxazoline compositions and methods of using same'
Example XVIII
So just for the record, MDAR was first synthesized and tested in 1962. It's not a particularly demanding target BUT it is SLIGHTLY more difficult than rubbish like p,4-dimethylaminorex (DMAR). I've mentioned this before but Dr. Dave was VERY clear that 4-methyl aminorex is an MAOI while aminorex is not. Unlike 4-MAR it does not have a trans-cis pair, simply (R) & (S) stereoisomers.
I'm just going through and providing people with firm reference for all of the facts that I have asserted. Synthesis discussion is not allowed but I think it's OK to say that we tried several routes and the Henry Reaction proved to be the best. Cyclization needs nasty things. Do not try this at home. I just forgot where the reference was until I used the appropriate search engine.
What is it like? Well I didn't taste it, but the reports suggest that it's an entactogen with a dose range similar to MDA. This makes sense, but in medicinal chemistry, their are often totally unexpected results when a ligand is even slightly modified. We refer to this as 'the magic methyl effect'. I remember one report which stated 'this is the greatest drug legal or illegal I have ever enjoyed'. A rare ++++ event.
We also tested 4-methylaminorex (PAR) & 3-methylaminorex (MAR). The former is almost exclusively active on SERT and is very subtle until very high doses are consumed. The latter appeared to be DAT>NET>>SERT. A 2:1 mixture of the 2 positional isomers produced effects almost identical to those produced by MDAR (based on reports who tried them all). I DID sample those 2 individually, as a 1:1 mixture and finally as a 2:1 mixture. We didn't like the fact that it required 2 compounds (twice as much potential for unexpected toxicity) and thus we pressed on to MDAR.
Aminorex has 5HT2b affinity so regular (daily) use can cause heart valve damage in just 28 days. It seemed that 5% of people suffered this fate but the other 95% showed no change in cardiac function whatsoever. We figured that people do not tend to take entactogens daily or multiple times a day, unlike stimulants.
I include a very good article on the 3D QSAR of aminorex derivatives:
Aminorex analogs - PMC
Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. ...
www.ncbi.nlm.nih.gov
Note how many chemists looked at the p-F homologue and thought 'wow - I can profit 4 times as much!!!' but the truth is, PFAR lasts too long for most people. We specifically went for the plain methyls because they act both to make the ligands selective but also serve as sacrificial moieties (groups designed to provide the body with a metabolic pathway not limited to a specific CYP liver enzyme). So their duration is about the same as MDMA/MDA.
Can one ring-substitute to provide significant 5HT2a affinity? Well oddly 2CB-Aminorex did turn up in Sweden in 2018. But reports suggest that it might have stimulant effects, but that is all. I think sekio suggested it was an internal standard although I note that someone tried adding the 2,5-dimethoxy-4-bromo moieties to just about every class of stimulant known. I mean, they did it to benzylpiperazine... That seems just reckless to me. What if it had proved to invoke irreversible 5HT2b binding (just an example)?
