chemrox
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N-(R1, R2, R3)benzylpiperazines
Shulgin suggested N-benzylpiperazine might serve as a basis for some new, interesting compounds. N-benzylpiperazine is an amphetamine like drug that
is completely legal at present. It is short acting and somehow falls short of what meth heads like. I don't use speed and happened to taste a little
BZP by accident while precipitating the diHCl. It gave me a speed rush that was thankfully over within a half hour. I don't know how much I tasted
but it couldn't have been more than a few mg.
The challenge is to make the 3,4,5 dimethoxy version or the 3,4 MeO2 analog. I just read a patent where the product, 2,4,6 benzylpiperazine was made
by reductive amination using H2 at 10 bars. This method doesn't appeal to me as it involves equpiment I don't have and don't want to make. A lot of
reasons for that including the attendant scrutiny that can come of operating such equipment and materials.
I do have NaBH3 and could make the cyanoborohydride from it. I'm thinking maybe this could work too but haven't done the literature search to see if
it's been tried. That should be the first step. Also my BZP is commercial so I haven't had occaision to make it.
Any thoughts or information?
Thanks,
chemrox
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Furch
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Not that it's OTC or anything, but I suggest you look into the use of substituted benzyl amines, which can be reacted in an SN2 manner with
bis(2-chloroethyl)amine ("nitrogen mustard", a variation of mustard gas).
Also, check out the phenylpiperazine, these seem to posess 5-HT activity... The phenylpiperazin variation of 2c-b has been synthesized and bioassayed
- active... I've got some 2,5-dimethoxy-4-chloroaniline lying around which could be made into the PP-variation of 2c-c.
- Furch
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stoichiometric_steve
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| Quote: | | Originally posted by FurchThe phenylpiperazin variation of 2c-b has been synthesized and bioassayed - active... |
would you mind giving us a REFERENCE for that? would be interesting. thanks.
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PainKilla
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J. Med. Chem. (1986) 29, 630-634
Attachment: jm00155a008.pdf (684kB)
This file has been downloaded 916 times
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Nicodem
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| Quote: | Originally posted by chemrox
N-benzylpiperazine is an amphetamine like drug that is completely legal at present. |
Wrong, it is scheduled in USA, Sweden, Australia and perhaps some other countries as well. It is however legal to poses in most of the world and
freely and cheaply available from chemical suppliers.
| Quote: | | I don't use speed and happened to taste a little BZP by accident while precipitating the diHCl. It gave me a speed rush that was thankfully over
within a half hour. I don't know how much I tasted but it couldn't have been more than a few mg. |
Wrong, 1-benzylpiperazine has a treshold of about 100 mg. Some might perceive certain activity signs as low as 50 mg, but in no way can anybody claim
activity from "a few mg". It also lasts for several hours and not just "a half hour". I suggest you to read a bit on the placebo effect to clear up
the confusion.
| Quote: | | The challenge is to make the 3,4,5 dimethoxy version or the 3,4 MeO2 analog. |
Do you mind explaining why would that be a challenge? The resulting 1-(3,4,5-trimethoxybenzyl)piperazine would not be a stimulant. Neither would it be
a psychedelic. Any activity that it might have would not be of particular interest to anybody I know. Apparently the SAR of 1-benzylpiperazines
follows the same rules as the pyrovalerone type of stimulants follow. Thus the 1-(4-methylbenzyl)piperazine is also just a stimulant while the
1-(4-methoxybenzyl)piperazine is nearly inactive up to 300 mg, and so on. To see how the aromatic substitution pattern governs the DA/NE/5-HT releases
in the pyrovalerone derivatives see J. Med. Chem., 49 (2006) 1420-1432 as well as US2004033349. From there on, you can plan some trully challenging 1-benzylpiperazine modifications.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Furch
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I would guess that different N-benzylpiperazines can be made by reductive amination of variations of benzaldehyde with piperazine, followed by
reduction with NaBH4, which you mentioned you had access to... At least that's what I think you ment. I.e. no need to make sodium cyanoborohydride...
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chemrox
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I don't understand that harsh sounding post. Its as though he revels in fiinding fault. And in being "right!" That aside, and ignoring the 'why do
I call it a challenge?' question, I really appreciate the information and references. I thought I had expressed my speculation that the phenyl ring
substituted analogs had been made.
Again, thanks for the refs. I'll come back to the thread when I've digested them.
I had no idea BZP had been scheduled. What a shame! Next they'll schedule nitrous. A few years ago I bought a half kilo of the stuff in 100 gram
bottles. I'm hoping it will prove useful sometime. Buying it was an impulse. I got some indole at the same time. I haven't gotten to it either but
I've been without a lab these many years. It is true joy to be doing wet chemistry again. Improvising in the kitchen didn't work very well and would
have lead to conflicts. A lot of people find ether fumes a bit intimidating. Imagine my wifes comments on a mercaptan being made in the same place
we cook our food.
I've been working on biodiesel related matters. Trying to improve on the ways people get rid of glycerides. I'm hopeful that a solid phase approach
to the 'catalyst' can be developed. I've been using column chromatography as model to test substrates. I've nothing to report having just started.
The main need is a "catalyst" that remains active or can be easily reactivated and can be used in line with the other fuel processing steps so the
whole process is continuous feed, continuous production. We've a long way to go yet before we can say what improvements are warranted and might be
feasible. My partner is a mechanical engineer. Anyway this is all way off topic and I beg indulgence.
I am not familiar with pyrovalerone agents, their history, properties and uses. What is the stimulant that is used by medics when someone has been
overdosed with depressants, if you know? Can you also direct me to references, other information on pyrovalerone stimulants. The only keto amines I
know about are the Khat alkaloids. I'm intrigued.
Do you know whether the phenylpropanolamines have been checked for activity? I would suspect they have since their syns are well documented and I
suppose the results have been less than inspiring.
[Edited on 28-1-2007 by chemrox]
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chemrox
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| Quote: | | [quote. To see how the aromatic substitution pattern governs the DA/NE/5-HT releases in the pyrovalerone derivatives see J. Med. Chem., 49
(2006) 1420-1432 as well as US2004033349. From there on, you can plan some trully challenging 1-benzylpiperazine modifications. |
Do you have a copy of J. Med. Chem., 49 (4), 1420 -1432, 2006. 10.1021/jm050797a S0022-2623(05)00797-1
Web Release Date: January 25, 2006
Copyright © 2006 American Chemical Society
1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) Analogues: A Promising Class of Monoamine Uptake Inhibitors
Peter C. Meltzer,* David Butler, Jeffrey R. Deschamps, and Bertha K. Madras
you could post or send?
(I haven't renewed my ACS membership for the year yet, waiting on payments)
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PainKilla
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The above:
Attachment: jm050797a.pdf (160kB)
This file has been downloaded 1264 times
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longimanus
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| Code: | What is the stimulant that is used by medics when someone has been overdosed with depressants, if you know? |
Maybe it's a little offtopic but... when reqested...
Bemegride (4-ethyl-4-methyl-piperidin-2,6-dione) - analeptic and stimulant (~equivalent to pemoline); used as antidote for barbiturate overdose
(together with artificial respiration and alkalinisation of urine).
Other respiratory stimulants with possible psychomotor stimulant properties are amiphenazole (2,4-diamino-5-phenylthiazole, pemoline analogue) and
doxapram [1-ethyl-4-(2-morpholin-4-ylethyl)-3,3-diphenyl-pyrrolidin-2-one].
And... I suppose flumazenil is not what chemrox was refering to.
[Edited on 28-1-2007 by longimanus]
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Nicodem
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| Quote: | Originally posted by chemrox
Do you know whether the phenylpropanolamines have been checked for activity? I would suspect they have since their syns are well documented and I
suppose the results have been less than inspiring. |
Of course they have been checked and their bioactivity is well documented. Actually, Ephedra sinensis which contains one of the simplest
1-phenyl-2-aminopropanols (ephedrine), was used medicinally for thousands of years in China. Its vasoconstrictive properties were known to the old
Romans. Nowdays, there are still numerous compounds of this structural class used as pharmaceuticals, so you can bet that the results were certainly
not less than inspiring. A multibillion worldwide business is based on the activity of such compounds!
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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chemrox
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I was thinking of the other kind of 'activity' ie psychedelic qualities. Phenylpropanolamine itself is probably a dangerous adulterant/contaminant in
garage amphetamine because of its vasoconstrictor/hypertenssive effects
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chemrox
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BTW- thanks for the refs to all that posted the ones I asked about
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chemrox
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| Quote: |
Bemegride (4-ethyl-4-methyl-piperidin-2,6-dione) - analeptic and stimulant (~equivalent to pemoline); used as antidote for barbiturate overdose
(together with artificial respiration and alkalinisation of urine).
Other respiratory stimulants with possible psychomotor stimulant properties are amiphenazole (2,4-diamino-5-phenylthiazole, pemoline analogue) and
doxapram [1-ethyl-4-(2-morpholin-4-ylethyl)-3,3-diphenyl-pyrrolidin-2-one].
And... I suppose flumazenil is not what chemrox was refering to.
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What do you suppose would be used in the case of a GHB "coma?"
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chemrox
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| Quote: | Originally posted by PainKilla
The above: |
Nice schematic!
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longimanus
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| Quote: |
I was thinking of the other kind of 'activity' ie psychedelic qualities.
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From "Serotonin Receptor Affinities of Psychoactive Phenalkylamine Analogues"; Glennon R.A., Liebowitz S.M., Anderson G.M.; J. Med. Chem.
1980, 23, 294-299:
| Quote: |
For example, the pA2 values for 1-(4-methoxyphenyl)-2-aminopropanol, 5.22 +/- 0.12, n = 3, and 1-(4-methylphenyl)-2-aminopropanol, 5.40 +/- 0.18, n =
4, do not differ subtantially from those of 10(1-(4-methoxyphenyl)-2-aminopropane, 5.15, +/- 0.04, n =
5) and 14(1-(4-methylphenyl)-2-aminopropane, 5.51, +/- 0.11, n = 2), while the
pA2 value for 1-(4-methoxyphenyl)-2-aminopropanol (43a), 4.90 +/- 0.10, n = 3, is considerably lower than the pA2 of the
corresponding 2,4-dimethoxyphenylisopropylamine (16)(5.60, +/- 0.08, n = 4).
Referential: mescaline - 5.65, +/- 0.10, n = 4
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Besides from the affinity-lowering interactions between the substituent on position 2 and the OH-group on
the aliphatic chain things do not seem to differ significantly between propanes and propanols.
| Quote: |
What do you suppose would be used in the case of a GHB "coma?"
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One hard question - possibly nothing: | Quote: |
One to 6 teaspoons of GHB taken with alcohol will result--within 15 to 30 minutes--in a pronounced coma and substantial respiratory depression
possibly necessitating intubation, said Texas toxicologist Todd. But within 1 to 2 hours, spontaneous recovery often occurs. "People have been in deep
coma in the emergency room and in the process of intubation will just sit up, spontaneously 'come right back to life,' and wonder why they're there.
There is amnesia about the experience," said Todd. She added, "This is a problem both in follow-up and to those who use the drug. It does not provide
a deterrent, since they don't really remember their near-death experience."
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From Coma-Inducing Drug GHB May Be Reclassified, Charles Marwick, JAMA - Medical News & Perspectives, Vol 277, May 21 1997, 1505-1506
GHB acts through two different receptors - specific GHB receptors and GABABR - so, either specific antagonists (not available as medicines), or the
beforementioned artificial respiration and maybe cardiac stimulation.
[Edited on 30-1-2007 by longimanus]
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phase_dancer
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Physostigmine has been successfully used to treat GHB overdose.
| Quote: | [Caldicott DGE, Kuhn M. Gamma-hydroxybutyrate overdose and
physostigmine: teaching new tricks to an old drug? Ann Emerg
Med. January 2001;37:99-102.]
Gamma-hydroxybutyrate was introduced as an anesthetic agent in the 1960s and is still used in some countries, despite recognized disadvantages. More
recently, it has emerged as a popular recreational drug. We report 3 cases of gamma-hydroxybutyrate overdose, the effects of which were reversed by
the administration of low-dose intravenous physostigmine. The origins of this regimen and the case for physostigmine as a potential antidote are
described.
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longimanus
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Tired of being off-topic!
| Quote: |
Physostigmine has been successfully used to treat GHB overdose.
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Hard to tell if "successfully" is the right word:
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As noted in the review by Traub et al, the evidence for and against the use of physostigmine is of poor quality. Only two papers (involving six
patients) are set in the emergency department, while those in the anaesthetic room are uncontrolled. This matters since the recovery from GHB induced
anaesthesia is relatively rapid and it is therefore difficult to draw conclusions from uncontrolled studies.
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From Gammahydroxybutyrate overdose and physostigmine; Allen L., and Alsalim W.; Emerg. Med. J., Apr 2006; 23: 300 - 301
And even more:
Physostigmine Does Not Effect Arousal but Produces Toxicity in an Animal Model of Severe g-hydroxybutyrate Intoxication; Theodore C. Bania and Jason
Chu; Acad. Emerg. Med., Mar 2005; 12: 185 - 189
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