Author Topic: Aminorex patents  (Read 3367 times)

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Megatherium

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Aminorex patents
« on: March 14, 2003, 05:29:00 PM »

Patent BE628803


Patent US3161650


Patent US3278382


Patent DE2101424



According to

https://www.thevespiary.org/rhodium/Rhodium/pdf/poos.aminorex-1.pdf

the p-halogen analogs of aminorex are more powerfull than plain aminorex:
* aminorex: ED50 = 5.8 mg / kg
* p-bromo aminorex: ED50 = 4.6 mg / kg
* p-chloro aminorex: ED50 = 2.5 mg / kg
* p-fluoro aminorex: ED50 = 1.2 mg / kg

Now, I presume it safe to say the p-halogen analogs of trans-4-MAR should also be stronger than unsubstituted trans-4-MAR.  Is there information about these trans-4-MAR analogs?

Megatherium

  • Guest
I think I have a pertinent question, is there...
« Reply #1 on: March 15, 2003, 06:13:00 AM »
I think I have a pertinent question, is there information about 4-methyl aminorex analogs with substituted phenyl rings.  Some bees have been talking about the MDMA variant of 4-MAR.  My question is, does 4-MAR and amphetamine + the psychedelic amines (DOM, MDMA, ...) target the same receptor?

It is rather curious that the fluoro analog of 4-MAR is more potent than 4-MAR & the p-fluoroamphetamine is less potent than regular amphetamice.  How to explain this?

Rhodium

  • Guest
Receptors for 4-MAR
« Reply #2 on: March 15, 2003, 08:19:00 AM »
It is not precisely known which receptor 4-MAR and analogs target, but it is clear that the serotonin system is involved to a greater degree than in the case of plain amphetamines.

Megatherium

  • Guest
Future 4-MAR halogen analogs of abuse
« Reply #3 on: March 15, 2003, 09:01:00 AM »
So, making a 4-MAR halogen analog would be  -pharmacologically speaking - a shot in the dark.

I got inspired by this:
 "Contrary to previously cited work this suggests that aminorex may in fact be as potent an adrenomimetic as amphetamine. In any case, Poos (personal communication) highlighted eight compounds which may have adrenomimetic activity similar to those of amphetamine and methamphetamine.

Shown below and listed in decreasing order of anoretic activity they are:

1) 2-amino-5-(4-fluorophenyl)-2-oxazoline
2) 2-amino-5-(4-Chlorophenyl)-2-oxazoline
3) 2-amino-5-(3-trifluoromethylphenyl)-2-oxazoline
4) 2-amino-5-(4-bromophenyl)-2-oxazoline
5) 2-amino-5-phenyl)-2-oxazoline [aminorex]
6) 2-amino-5-(4-trifluoromethylphenyl)-2-oxazoline
7) 2-dimethylamino-4-methyl)-5-phenyl-2-oxazoline
8) 2-amino-4-methyl-5-phenyl-2-oxazoline [4-methylaminorex].

Although not mentioned in this work, one would immediately assume that the 4-fluoro- and 4-chloro-phenyl derivatives of compounds 7 and 8 would also have significant anoretic activity. Given the astoundingly simple synthetic process required to produce these compounds, and the fact that the 4-halogen substituted aryl derivatives would require precursors unlikely to titillate the interest of law enforcement agencies, these compounds will most probably be made in future clandestine syntheses. It is also conceivable that some enterprising clandestine chemist will wonder if appropriately substituted methoxy derivatives will have psychotomimetic properties. "

From:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/future_drugs.html



Rhodium

  • Guest
Please refrain from the chloro/bromo/iodo analogs
« Reply #4 on: March 15, 2003, 09:40:00 AM »
Before any information comes to light which would indicate otherwise, I would be wary of testing any halo-aminorex analogs with the exception of the 3- or 4-fluoro analogs, taking the well-known neurotoxicity of 4-haloamphetamines into account.

pHarmacist

  • Guest
Fluoro
« Reply #5 on: March 15, 2003, 09:42:00 AM »
Besides, the fluoro analogs would probably bee of decreased potency.


Rhodium

  • Guest
Not so...
« Reply #6 on: March 15, 2003, 09:55:00 AM »
Not so, according to the table in

Post 417317

(Megatherium: "Future 4-MAR halogen analogs of abuse", Methods Discourse)
p-Fluoro-4-MAR is the most potent of them all...

pHarmacist

  • Guest
neurotox
« Reply #7 on: March 15, 2003, 11:40:00 AM »
But why do you think then that halo-aminorex analogs with the exception of the 3- or 4-fluoro analogs may bee neuro-toxic? This familly of compound obviously don't follow the same pattern as amphetamines since 4-fluoro analog of amphetamine is less potent. Or am I too stoned on benzos to post?


Megatherium

  • Guest
Here are some further refs.
« Reply #8 on: March 15, 2003, 12:00:00 PM »
Here are some further refs. about 4-MAR:

* French Patent M2448
* Archives Int Pharmacodyn Ther 164(2), 412-18 (1966)
* J Pharmacology and Experimental Therapeutics 140:367-374 1963
* Ibid. 141:180-184 1964
* J Clinical Pharmacology 7:296-302 1967
* Science 218(457) 487-490 1982
* Annual Review of Med Chem 51-58 1965, 44-47 1966


Am I right to presume that p-fluoro benzaldehyde (with the appropriate base catalyst) will react in the same way with nitroethane to the nitroalcohol, or is the chance higher that water eliminates forming the nitropropene?
Then a reduction with Zn / AcOH will follow to reduce the nitro.  Such an easy synthesis, this is kids stuff.

SPISSHAK

  • Guest
According to the information I have
« Reply #9 on: March 15, 2003, 12:52:00 PM »
The nitroalcohol is stable so long as the temperature does'nt excedd 40 degress centigrate, and the reaction (the addition reaction between nitro alkane, and benzaldehyde) is not quenched with a strong acid.
I've seen examples where a strong acid like h2so4 is employed along with Zinc as a reduction system, in this case they add the acid dropwise the Zinc has to be a certain mesh size (80) I think so it will react expidiently with the strong acid, and the mixture has to be stirred well to avoid localized low PH, and the temperature is not to excedd 40 degress.

Rhodium

  • Guest
Neurotox
« Reply #10 on: March 15, 2003, 01:10:00 PM »
pHarmacist: I do not hold any strong opinion about the para-halogen 4-MAR analogs being neurotoxic as they are not immediate analogs of the corresponding amphetamines, they are just related. But until it has been proven in some way that they are not neurochemically similar, I think it is a very good idea to assume that they may be, and therefore stay away from them. It is gratis to avoid possibly harmful analogs, while the price of trying them out may be high. The psychonaut profession is dangerous enough even without taking any unnecessary risks.

The reason I exclude the fluoro derivatives is that the fluoroamphetamine congeners has been shown not to pose the risks associated with the other halogens, and that fluorine generally does not behave as a halogen

bioisostere

(http://www.chem.qmul.ac.uk/iupac/medchem/ah.html#b2).

pHarmacist

  • Guest
Better safe than sorry
« Reply #11 on: March 15, 2003, 01:28:00 PM »
Now I see what you meen Rhodi, of course, one should not fuck around with potential neurotoxins. I guess we'll have to see if Nemo_Tenetur have tried them yet  ;)


Nemo_Tenetur

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Synthesis planned but not yet tried ...
« Reply #12 on: March 25, 2003, 12:52:00 AM »
I`ve planned the synthesis and even the precursors aquired, but not yet tried. IMHO, the main problem is to get 1-(4-fluorophenyl)-2-aminopropan-1-ol of sufficient purity. My proposed synthetic pathway was to brominate para-fluoropropiophenone (commercially available), which I`ve done some years ago successful for the synthesis of 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)propan-1-one. Then reaction of the bromoketone with potassium phthalimide followed by hydrolysis which I`ve never done followed by reduction. I guess it wouldn`t be easy to purify the intermediate due to easy pyrazine formation.

Megatherium

  • Guest
EP0960876
« Reply #13 on: March 25, 2003, 04:40:00 AM »
This seems to bee a nice patent to get the precursor (after a Zn / AcOH or H2SO4 reduction of the nitoalcohol) with the right stereospecific requirements for the KOCN reaction:

Patent EP0960876

   (curtsy to Barium  :) )

Keep us informed about the bioevalutation of that 4-MAR analog.  I am pretty interested.

Bandil

  • Guest
4-methylAR vs. AR
« Reply #14 on: October 13, 2003, 02:26:00 AM »
According to the

document

(https://www.thevespiary.org/rhodium/Rhodium/pdf/poos.aminorex-1.pdf), which Megatherium reffers to, aminorex seems more potent that 4-methylaminorex. I always had some idea in my twisted brain, that the methyl version was more potent?

Does anyone have some information on the subjective effects of aminorex compared to the methylated version? Does it even make sense to try out the 4-methyl version of the para-fluoro analogue, when the unmethylated version theoretically is more potent?

Regards
Bandil


Rhodium

  • Guest
Apples & Oranges
« Reply #15 on: October 13, 2003, 06:33:00 AM »
Poos measured the anorexiogenic activity, not the CNS stimulant activity. And the plain aminorexes, as well as the 3,4-dimethylaminorexes seems to be more toxic anyway...

Assholium

  • Guest
aminorex vs. 4--MAR
« Reply #16 on: October 13, 2003, 12:59:00 PM »
Does anyone have some information on the subjective effects of aminorex compared to the methylated version?

I tried aminorex - it's a pretty strong stimulant, 40 mg of fumarate gives very hard stimulation with duration about 8-9 hrs. 50 mg of meth racemate gives compared, but twice longer buzz, and 100 mg of 4-MAR - only very, very light excitation.

josef_k

  • Guest
As I think someone else has mentioned Aminorex
« Reply #17 on: October 13, 2003, 01:13:00 PM »
As I think someone else has mentioned Aminorex can cause pulmonary hypertension, which you can die from. Perhaps a couple of doses cause no harm, but if you would take it regulary, you're just asking for trouble. Check out this article on medline:

Medline (PMID=3928246)



Also I remember reading about a family where one by one all the family members got this condition and they couldn't understand why, until they found out that they had an aminorex lab...

Therefore I think you should think twice before trying it.

Megatherium

  • Guest
Also I remember reading about a family where...
« Reply #18 on: October 13, 2003, 03:01:00 PM »
Also I remember reading about a family where one by one all the family members got this condition and they couldn't understand why, until they found out that they had an aminorex lab...

That would be

Post 456788

(Megatherium: "A word of caution ...  & another KOCN patent", Methods Discourse)


It is my understanding that the aminorex appetite supressant was withdrawn from the pharmaceutical market because of these pulmonary side effects.

Megatherium

  • Guest