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All 20 posts Subject: Aminorex patents Please login to post Down

Megatherium
(Hive Bee)
03-15-03 01:29
No 417144
      Aminorex patents

Patent BE628803
Patent US3161650
Patent US3278382
Patent DE2101424

According to https://www.rhodium.ws/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
(Hive Bee)
03-15-03 14:13
No 417272
      I think I have a pertinent question, is there...

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
(Chief Bee)
03-15-03 16:19
No 417304
User Picture       Receptors for 4-MAR

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
(Hive Bee)
03-15-03 17:01
No 417317
      Future 4-MAR halogen analogs of abuse

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.rhodium.ws/chemistry/future_drugs.html

Rhodium
(Chief Bee)
03-15-03 17:40
No 417322
User Picture       Please refrain from the chloro/bromo/iodo analogs

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
(Hive Addict)
03-15-03 17:42
No 417324
User Picture       Fluoro

Besides, the fluoro analogs would probably bee of decreased potency.

Accept No Imitations, There Can Only Bee One; www.the-hive.ws

Rhodium
(Chief Bee)
03-15-03 17:55
No 417326
User Picture       Not so...

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
(Hive Addict)
03-15-03 19:40
No 417360
User Picture       neurotox

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?

Accept No Imitations, There Can Only Bee One; www.the-hive.ws

Megatherium
(Hive Bee)
03-15-03 20:00
No 417367
      Here are some further refs.

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
(Hive Addict)
03-15-03 20:52
No 417372
      According to the information I have

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
(Chief Bee)
03-15-03 21:10
No 417380
User Picture       Neurotox

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
(Hive Addict)
03-15-03 21:28
No 417387
User Picture       Better safe than sorry

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 wink

Accept No Imitations, There Can Only Bee One; www.the-hive.ws

Nemo_Tenetur
(Analogue Bee)
03-25-03 08:52
No 421074
      Synthesis planned but not yet tried ...

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
(Hive Bee)
03-25-03 12:40
No 421104
      EP0960876

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 smile )

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

Bandil
(you can always take some more)
10-13-03 09:26
No 464374
      4-methylAR vs. AR

According to the document (https://www.rhodium.ws/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

I just love the smell of bromine in the morning!

Rhodium
(Chief Bee)
10-13-03 13:33
No 464400
User Picture       Apples & Oranges

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
(Гуру)
10-13-03 19:59
No 464470
      aminorex vs. 4--MAR

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
(Hive Bee)
10-13-03 20:13
No 464475
      As I think someone else has mentioned Aminorex

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
(Hive Bee)
10-13-03 22:01
No 464494
      Also I remember reading about a family where...

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
(Hive Bee)
10-17-03 10:53
No 465174
      aminorex & pulmonary hypertension

http://dec51.lf2.cuni.cz/~hampl-v/english/hampl/vhdex.htm

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	All 20 posts		Subject: Aminorex patents		Please login to post		Down


		Megatherium (Hive Bee) 03-15-03 01:29 No 417144				Aminorex patents
						Patent BE628803 Patent US3161650 Patent US3278382 Patent DE2101424 According to https://www.rhodium.ws/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 (Hive Bee) 03-15-03 14:13 No 417272				I think I have a pertinent question, is there...
						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 (Chief Bee) 03-15-03 16:19 No 417304				Receptors for 4-MAR
						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 (Hive Bee) 03-15-03 17:01 No 417317				Future 4-MAR halogen analogs of abuse
						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.rhodium.ws/chemistry/future_drugs.html



		Rhodium (Chief Bee) 03-15-03 17:40 No 417322				Please refrain from the chloro/bromo/iodo analogs
						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 (Hive Addict) 03-15-03 17:42 No 417324				Fluoro
						Besides, the fluoro analogs would probably bee of decreased potency. Accept No Imitations, There Can Only Bee One; www.the-hive.ws



		Rhodium (Chief Bee) 03-15-03 17:55 No 417326				Not so...
						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 (Hive Addict) 03-15-03 19:40 No 417360				neurotox
						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? Accept No Imitations, There Can Only Bee One; www.the-hive.ws



		Megatherium (Hive Bee) 03-15-03 20:00 No 417367				Here are some further refs.
						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 (Hive Addict) 03-15-03 20:52 No 417372				According to the information I have
						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 (Chief Bee) 03-15-03 21:10 No 417380				Neurotox
						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 (Hive Addict) 03-15-03 21:28 No 417387				Better safe than sorry
						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 Accept No Imitations, There Can Only Bee One; www.the-hive.ws



		Nemo_Tenetur (Analogue Bee) 03-25-03 08:52 No 421074				Synthesis planned but not yet tried ...
						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 (Hive Bee) 03-25-03 12:40 No 421104				EP0960876
						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 (you can always take some more) 10-13-03 09:26 No 464374				4-methylAR vs. AR
						According to the document (https://www.rhodium.ws/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 I just love the smell of bromine in the morning!



		Rhodium (Chief Bee) 10-13-03 13:33 No 464400				Apples & Oranges
						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 (Гуру) 10-13-03 19:59 No 464470				aminorex vs. 4--MAR
						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 (Hive Bee) 10-13-03 20:13 No 464475				As I think someone else has mentioned Aminorex
						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 (Hive Bee) 10-13-03 22:01 No 464494				Also I remember reading about a family where...
						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 (Hive Bee) 10-17-03 10:53 No 465174				aminorex & pulmonary hypertension
						http://dec51.lf2.cuni.cz/~hampl-v/english/hampl/vhdex.htm

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