(Hive Addict)
07-23-03 20:29
No 449302
(Rated as: good read)
I haven't ever posted in this forum b4, the reason being I don't have enough knowledge. I did find this paper today though (I assume some of you have read it before). It is a more potent analog of cocaine that is discussed in the article. It is not discussed in Beagle's paper on coke analogs, but looks like it would have a relatively similar method of synthesis. Looks incredibly difficult to synth for the typical clandestine chemist, but just hoping to hear what you all have to say about it.
Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors
by
Tamiz AP, Zhang J, Flippen-Anderson JL, Zhang M,
Johnson KM, Deschaux O, Tella S, Kozikowski AP
Drug Discovery Program,
Institute of Cognitive and Computational Science,
Georgetown University Medical Center,
3970 Reservoir Road, NW,
Washington,
DC 20007-2197, USA.
J Med Chem 2000 Mar 23; 43(6):1215-22
ABSTRACT
The synthesis and monoamine transporter activity of additional members of a series of 3,4-disubstituted piperidines (truncated analogues of the WIN series) are described. All members of this series were prepared from arecoline hydrobromide in optically pure form and were evaluated for their ability to inhibit high affinity uptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) into rat brain nerve endings (synaptosomes). Most of the compounds prepared in this series are reasonably potent DAT inhibitors (K(i) values of 4-400 nM) and have selectivity for the 5-HT transporter relative to both the NE transporter (3-9-fold) and to the DAT ( approximately 25-fold). In the present series, (-)-methyl 1-methyl-4beta-(2-naphthyl)piperidine-3b
Rainbows & Butterflies Forever :)
(Chief Bee)
07-24-03 07:05
No 449423
(Rated as: good read)
Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors
Tamiz AP, Zhang J, Flippen-Anderson JL, Zhang M, Johnson KM, Deschaux O, Tella S, Kozikowski AP
J. Med. Chem. 43(6), 1215-22 (2000) (../rhodium/pdf /cocaine.pipe
Interesting - this paper is the second part of the infamous one which gives the prep of a potent cocaine analog from arecoline and p-Cl-PhMgBr, described in Post 329686 (Rhodium: "Precious metals & Crack", General Discourse) and the full ref is found in the doc linked in Post 357128 (Rhodium: "Arecocaine", Novel Discourse).
Other Cocaine Analogs:
Post 444618 (Rhodium: "Dopamine Transporter SAR of Tropanes", General Discourse)
Post 440396 (Rhodium: "Novel Sigma-1/DAT ligands", General Discourse)
(Stranger)
07-24-03 16:48
No 449528
It's mentioned Post 212069 (monkpea: "Re: Structurally simple cocaine analogs -Beagle", Novel Discourse) that at least one analogue should produce a numbing effect similar to standard cocaine. Does this hold true for all of them?
I've used TFSE a fair bit, but haven't come up with anything definite - did anyone ever take Rhodium up on his challenge Post 329415 (Rhodium: "I feel there are TOO many coincidences now...", General Discourse)?
It seems like there's a tremendous amount of information about cocaine analogues out there, but no reports of successful (or even, as far as I can tell, attempted synthesis.
(Chief Bee)
07-24-03 18:37
No 449552
The first cocaine analog synthesis attempt whatsoever I've seen at the Hive is the one posted in Post 446941 (tropine: "Arecoline analogue...freebase success! But....", Serious Chemistry)
(Hive Addict)
07-24-03 23:48
No 449621
The arecoline success cheered me greatly. Now, Rhod's challenge I wish I could take up, but I only have the knowledge for basic chem. SWIM has access to 99%+ white. It's unfortunate I wouldn't know how to tell him to do the procedure. Could anybody explain the procedure so that it's somewhere between theory and procedure. SWIM may be willing to play with a small cashwad of white to do this. What is the potency jump supposed to be? Guesses?
Rainbows & Butterflies Forever :)
(Chief Bee)
07-28-03 00:53
No 450252
(Rated as: good read)
First, you are supposed to turn the cocaine into anhydroecgonine, for example according to the instructions in this article:
An Improved Synthesis of (+)-2-Tropinone
Chunming Zhang, Stacey A. Lomenzo, Charles J. Ballay II, and Mark L. Trudell
J. Org. Chem. 62(22), 7888 - 7889 (1997) (../rhodium/pdf /anhydroecgon
DOI:10.1021/jo9710083
Then you use that, together with the procedure from the article in Post 221796 (Rhodium: "Re: 4-fluorophenyl cocaine analog", General Discourse), which is a grignard addition of 4-fluorophenylmagnesium bromide to the formed anhydroecgonine (this article also describes the preparation of anhydroecgonine). Have you performed a grignard reaction before?
The 1973 article by Clarke (Post 330321 (Rhodium: "Zorro: The yield minus the losses in each step, ...", General Discourse)) also describes the reaction, and tells us that Compound 13, which is the one we are interested in, is approximately 60x more effective than cocaine on a weight basis to induce "locomotor activity" in mice... To read the *.djvu article in the post above, check out Post 330098 (Rhodium: "What is DejaVu?", General Discourse)
Another 30 para-substituted phenyltropanes made from anhydroecgonine can be found in Table 2, together with binding data here: ../rhodium/pdf /cocaineanalog
(Hive Addict)
07-28-03 00:58
No 450254
Honestly, no solid evidence that this is the "supercoke," but sounds like fun, and quite a challenge, I am currently between countries, so it will be a little bit, but with help from a certain bee and some slow reconstruction of my lab in my new residence, I hope to crack this case. Any help is always appreciated.
Rainbows & Butterflies Forever :)
(Newbee)
07-29-03 00:34
No 450471
As best I know, there's no OTC source for 4-fluorophenylmagnesium bromide. (I'd be quite pleased if someone corrected me) So you'd either be synthing it as well, or ordering it from a chem co. Now, I don't think that'd be a big problem for most people, as as best I know it's not particularly watched. But for those of us who wish to avoid all unwanted attention, it could be a problem.
(Chief Bee)
07-29-03 03:19
No 450491
The whole procedure from cocaine to the 4-Fluorophenyltropane (including the preparation of the 4-Fluorophenylmagnesium bromide from p-Fluorobromobenzene) can be read on page 14 of Patent EP604354 - but the language is extremely technical.
(Hive Bee)
07-29-03 21:40
No 450592
Is that a kind of 1,4 Addition?
The only purpose of your life may be to serve as a warning to others http://www.despair.com
(Chief Bee)
07-29-03 23:43
No 450606
Yes, and I know that the details are discussed in another thread on this topic.