07-12-04 17:38
No 518920
I have been trying to gather information on 3-methylfentanyl and I have some questions that I cannot find the answers to.
1. What is the therapeutic index of 3-methyfentanyl?
2. I read on some german website that 3-methyfentanyl is highly hypnotic and toxic. Is this true?
... and no, I have no interest in synthesizing anything. Just so you know.
Thank you.
(Stranger)
07-12-04 21:55
No 518944
According to the first publication on the subject the Thepeutic Index (LD50/ED50) of methylfentanyl is 1662; of fentanyl - 255; morphine - 75.6; pethidine - 4.89. It can be read in J. Med. Chem. 1974, v. 17, No10, the exact page is 1050. By a strange coincidence I have the paper wright now on my desk. But this impressive and highly optimistic safety margin was obtained from rat data which, sincerely said, are a little more than useless when speeking about humans. All opiates, including fentanyls, are very different for humans (they feel them like ... like opiates) and for rodents (they feel them rather like stimilants). All fentanyl derivatives have a specific effect on humans, especially when introduced i.v. - transitory paralysis of breathing. It's not the usual opiate respiraty depression; with fentanyls it's brief but in many cases fatal. It is occuring only during I.V. administartion and you will guess that it is not the usual method for drug administration on lab rats but unfortunately is typical for humans. I have not used fentanyls myself but I have friends who have used simple fentanyl and they will be very sceptic on their high safety margin. At least in humans. Be very carefull when interpreting lab rat data!
(Chief Bee)
07-12-04 22:11
No 518948
According to Casy & Parfitt's book "Opioid Analgesics", this article will contain all the data you want, in detail.
N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpr
Van Bever WF, Niemegeers CJ, Schellekens KH, Janssen PA., Arzneimittelforschung. 1976;26(8):1548-51.
Medline (PMID=12771)
The intravenous analgesic activity and toxicity of a novel series of N-[4-substituted 1-(2-arylethyl)-4-piperidinyl]-N-phenylp
____ ___ __ _
Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs.
Niemegeers CJ, Schellekens KH, Van Bever WF, Janssen PA., Arzneimittelforschung. 1976;26(8):1551-6.
Medline (PMID=12772)
Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethy
____ ___ __ _
Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives.
Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ., Sci Sin. 1981 May;24(5):710-20.
Medline (PMID=6264594)
In the present paper, the synthesis and analgesic activity (mice, i.p. hot plate test) of the derivatives of 3-methyl fentanyl are briefly described. Compound 7302, cis-N-[1-(2-hydroxy-2-phenylethyl)-3-met
The Hive - Clandestine Chemists Without Borders
07-12-04 22:50
(Rated as: UTF PM Function)
(Newbee)
07-16-04 03:51
No 519679
As some of you know, I'm writing a book(fiction) and it deals with conspiracies, drugs etc.
I just need confirmation on a few ideas... or is the idea too far fetched?
Although I've read this in posts (After using TFSE), I just need confirmation...
What if someone accidentally poured say 5 ml of liquid with a narcotizing dose of 3-methylfentanyl or something equally potent (carfentanil) on his or her skin, would the person become high etc. (ie. get the effects of the substance)? My uneducated guess would be yes, he would as the amount needed is so small that it would be absorbed almost instantaneously.
Your help will be appreciated. Thank you.
07-20-04 05:54
(Rated as: UTFSE!)
07-20-04 18:28
(Rated as: UTFSE!)
07-21-04 03:17
(Rated as: insignificant)
(Newbee)
07-30-04 04:27
No 522597
Umm, I did, If you noticed, I even mentioned that in the posts. I cannot find any info on synethising N-phenethyl-3-methyl-peiperidone-4 from piperidone-4(monohydrochloride). I asked whether one solution I thought of was correct... and all I get is UTFSE? Believe me, I did.
What the fuck are you guys smoking??? Rate this as insignificant too. Thats all you fucked up high and mighty sanctimoneous moderators do anyway... Instead of giving a helping hand, you keep saying use the fucking search engine... I didn't ask, give me the recipe of such and such, or make xyz for me, I asked for pointers or documents that can show me the way.
I used to think of you guys as being chemists who are open to questions and helping newbies not up to your standards to better understand this subject, but you guys are not. You gys act like highschool kids with their own cliques where outsiders are harshly treated. Some of you really act like immature pricks.
What are you going to do now, ban me because you consider me an annoyance in your perfect little totalitarian world? I expect as much now. (I'll withhold the name calling the moderator deserves.)
Again, this is the question In asked, maybe my FSE skills aren't up to par.
"Could someone tell me or point me to any doc that explains how one would get N-phenethyl-3-methyl-piperidone-4 from 4-piperidone ?"
I checked again, and the FSE doesn't come up with any doc which contains anywhere near this answer.
(Hive Bee)
07-30-04 05:05
No 522606
What I found:
Post 438010 (pHarmacist: "Substituted N-Phenylpropanamides", Novel Discourse)
Post 60132 (Rhodium: "N-phenylethyl-4-piperidones via acrylates", Chemistry Discourse)
Dunno NOTHING about opioid/fentanyl chemistry, but TFSE turned up LOADS of even whole threads about the topic when searching for "3-methylfentannyl"...
I SERIOUSLY doubt that all those texts are only about its pharmacology!!!!
Greetz A
Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!
(Chief Bee)
07-30-04 06:40
No 522634
This is what I understand:
For N-phenethyl-piperidone-4, 4-piperidone, acetonitrile and phenethylbromide is used... right?
Yes, see the reaction diagram in ../rhodium /fentany
4-Piperidone is alkylated with phenethylbromide in acetonitrile solution to give N-phenethyl-4-piperidone (abbreviated NPP in the diagram).
So would one be able to synthesize N-phenethyl-3-methyl-piperidone-4 by using methylethylketone instead of acetonitrile?
Your question does not make any sense - acetonitrile just acts as a solvent in this reaction. By what kind of reasoning did you arrive at this proposal?
Again, this is the question In asked, maybe my FSE skills aren't up to par.
"Could someone tell me or point me to any doc that explains how one would get N-phenethyl-3-methyl-piperidone-4 from 4-piperidone ?"
I checked again, and the FSE doesn't come up with any doc which contains this answer.
Of course not - there is no such thing! If you compare their structures you see that you would need to attach a methyl group next to the carbonyl to arrive at your target compound, and that chemical transformation only looks good on paper...
If you research general preparations of 4-piperidones (something which would be very reasonable to do if you are contemplating this kind of chemistry) you will soon discover that the available routes are rather few, the most important being the following:
Michael Reaction:
Post 60132 (Rhodium: "N-phenylethyl-4-piperidones via acrylates", Chemistry Discourse)
Mannich Reaction:
Post 496728 (Megatherium: "Discussing the Mannich reaction", Serious Chemistry)
Post 481189 (josef_k: "You can use this method to use the the mannich", Newbee Forum)
via Allylsilanes:
Post 411081 (thallium: "Total Synthesis of Fentanyl", Novel Discourse)
Post 411082 (thallium: "RESULTS AND DISCUSSION Our synthetic approach...", Novel Discourse)
The Hive - Clandestine Chemists Without Borders
(Newbee)
07-30-04 07:27
No 522643
"Of course not - there is no such thing! If you compare their structures you see that you would need to attach a methyl group next to the carbonyl to arrive at your target compound, and that chemical transformation only looks good on paper..."
See, a simple answer with an excellent explanation which made me realize that I misunderstood a lot of the docs I've read and clearly shows my lack of real world knowledge. Now I understand a lot more and know what stuff to reread. Thank you.
P.S. - I have gone through all the links the 2 of you have provided before I posted my question, but being naive, I thought the piperidone-4 route was possible and was asking about that. Now Rhodium has answered the question elegantly.
(Hive Addict)
07-30-04 19:14
No 522728
Bee careful in your dreams. I seem to remember reading somewhere that the potency of these 3-substituted fentanys being more potent by weight than LSD. Just a dab will DO ya. Just remember, do spelled backward is od.
(Hive Bee)
10-11-04 14:00
No 535334
(Rated as: excellent)
The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues
M. D. Ivanovic, I. V. Micovic, S. Vuckovic, M. Prostran, Z. Todovic, V. D. Kiricojevic, J. B. Djordjevic and LJ. Dosen-Micovic
J. Serb. Chem. Soc. 69(7), 511–526 (2004)
Abstract
A general, five step method for the synthesis of 3-alkylfentanyl analogues (i.e., cis and trans 3-alkyl-4-anilidopiperidines 6.1–6.6) has been developed. The starting N-phenethyl-4-piperidone 1 was first converted into the cyclohexylimine derivative 2, alpha-deprotonated with butyllithium and the resulting imine anion efficiently monoalkylated with primary and secondary alkyl halides. After mild acid hydrolysis, the obtained 3-alkyl-4-piperidones 3.1–3.6 were isolated in good yields (79–85 %), then condensed with aniline to form imines 4.1–4.6. Subsequent reduction of the imines (LiAlH4/THF) yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.1–5.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.1–5.6 (29–51 % yield) and trans 5.1–5.6 (19–27 % yield), with the cis/trans ratio in the range 7/3–6/4. The synthesis was concluded by N-acylation of the purified 5.1–5.6, with propionyl chloride, to afford cis and trans 3-alkyl-4-anilidopiperidines 6.1–6.6 (~95 % yield, as monooxalate salts). No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the 1H-NMR spectra. Of the twelve synthesized 3-alkylfentanyls, ten compounds (two known and eight novel derivatives, all as the monooxalate salts) were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (±)-cis-3-Me fentanyl 6.1cis, (8 × fentanyl), and the novel (±)-cis-3-Et fentanyl 6.2cis, (1.5 × fentanyl), all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure-activity relationship (SAR) in this series of derivatives have been made.
Full text available for free at: http://www.shd.org.yu/htdocs/shd/Vol69/N