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Author: Subject: longer lasting cocaine analog
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[*] posted on 10-9-2006 at 04:59
longer lasting cocaine analog


cocaine is an ester of tropinol and benzoic acid which is rapidly metabolized by endogenous esterases in the body. maybe the ester linkage (-O-CO-)could be replaced by (-C-CF2-) or some other linkage to increase duration without significantly changing the effects of the compound
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[*] posted on 10-9-2006 at 10:34


Further evaluation of the reinforcing effects of the novel cocaine analog
2b-propanoyl-3b-(4-tolyl)-tropane (PTT) in rhesus monkeys

&roles:Anne M. Birmingham · Susan H. Nader Kathleen A. Grant · Huw M. L. Davies Michael A. Nader
Psychopharmacology (1998) 136:139–147



(2b-Propanoyl-3b-(4-tolyl)-tropane (PTT))


Excerp
.............2b-Propanoyl-3b-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the interinjection interval would influence the reinforcing effectsof PTT.



[Edited on 10-9-2006 by solo]

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[*] posted on 11-9-2006 at 08:39


Taken from a post by Fastandbulbous at bluelight.ru:
http://www.bluelight.ru/vb/showthread.php?t=171971&page=...



"The 3-alpha-phenyltropane with an acetylated 2-hydroxy group in the axial position has been assessed as being 60x the potency of cocaine, with a fairly similar pharmacological profile (ie abusable, unlike the Win series compounds with an axial 2-methylcarboxyl group). I remember reading that the unesterified compound is less active, but still moreso than cocaine. The OH goup must be axial to the ring though, or its potency becomes a fraction of that of cocaine's.

The last two are very simple compounds that are esters of pseudotropine. The benzoate ester is also known as tropacocaine and has a potency of about 0.1x that of cocaine. replacing benzoic acid with 4-fluorobenzoic acid gives a compound of aprox 0.4x the potency of cocaine; considering how easy it is to synth (and not from monitored reagents - you can actually start from atropine and get to 3-pseudotropyl 4-fluorobenzoate in a few easy steps), I'm really surprised that it hasn't shown up in street cocaine. Maybe the market is so saturated that no one thinks it's economically viable."

I've heard rumours about 4-fluorotropacocaine, albeit less potent, being qualitatively very similar to cocaine and longer lasting.

I'm afraid I cannot substantiate these rumours though...




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[*] posted on 11-9-2006 at 10:52


Compounds affecting the CNS part 4: 3-beta-phenyltropane-2-carboxylic acid esters and analogs.
R. Clarke et al., J. Med. Chem. (1973) 16, 11, 1260
http://www.erowid.org/archive/rhodium/pdf/cocaine.analogs.cl...

Chemistry, design and structure-activity relationship of cocaine antagonists.
Chem Rev 100 (2000) 925-1024
http://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf

Chemistry and Pharmacology of the Piperidine-Based Analogues of Cocaine.
Identification of Potent DAT Inhibitors Lacking the Tropane Skeleton.
J. Med. Chem. 1998, 41, 1962-1969
http://www.erowid.org/archive/rhodium/pdf/cocaine.analog.are...

Further SAR Studies of Piperidine-Based Analogues of Cocaine. 2. Potent
Dopamine and Serotonin Reuptake Inhibitors.
J. Med. Chem. 2000, 43, 1215-1222
http://www.erowid.org/archive/rhodium/pdf/cocaine.piperidine...


Tropinone is synthesized by the Mannich reaction, using succinic dialdehyde, methylamine and acetone dicarboxylic acid (= 3-oxopentanedioic acid).

Tropinone was first synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I.

Apparantely he also got some results from using acetone instead of acetone dicarboxylic acid when very alkaline conditions are employed.

ref = J. Chem. Soc. 111 (1917) 766

Also see:
J. Am. Chem. Soc. 68 (1946) 1608
http://rapidshare.de/files/32766266/Tropanone_and_its_homolo...
http://www.erowid.org/archive/rhodium/chemistry/cocainesynth...

Justus Liebigs Ann. Chem. 518 (1935) 1, 25
Eur. J. Med. Chem. Chim. Ther. 19, 2 (1984) 105-110


Reduction of tropinone yields a mixture of tropine (mp 63°C) and pseudotropine (mp 109°C). This paper discusses the yield of tropine and pseudotropine under varying conditions of reduction: Tetrahedron 6 (1959) 319
(it also details the separation of both stereoisomers via their gold salts)


Synthesis of succinic dialdehyde from pyrrole via succinaldoxime:
J. Am. Chem. Soc. 68 (1946) 1608
http://rapidshare.de/files/32766266/Tropanone_and_its_homolo...
http://www.erowid.org/archive/rhodium/chemistry/cocainesynth...

Succinic dialdehyde can also be prepared by passing a mixture of THF and O2 over a silver or copper catalyst at 350°C: US2710883
http://rapidshare.de/files/32773413/Succinaldehyde_manufactu...

2,5-dimethoxytetrahydrofuran by anodic oxidation of malic acid:
http://rapidshare.de/files/32757753/malic_acid_anodic_oxidat...

Succinic dialdehyde from diethyl succinate, ethyl formate and sodium in toluene:
Zh. Obshch. Khim. 28 (1958) 1097, 1099; english edition (J. Org. Chem. USSR) pages 1065, 1067


Acetone dicarboxylic acid from treating anhydrous citric acid with conc. H2SO4:
Ann.Chim.applic. 28 (1938) 297; Chem. Zentralbl. 110, I (1939) 1163

Chem. Ber. 17 (1884) 2542
http://rapidshare.de/files/32773099/Ueber_die_Acetondicarbon...

Justus Liebigs Ann. Chem. 261 (1891) 155
Indian J. Chem. Sect. B 43, 8 (2004) 1774 - 1778
Indian J. Chem. Sect. B 20, 6 (1981) 500-502
Justus Liebigs Ann. Chem. 422 (1921) 11
J. Chem. Soc. 121 (1922) 1644

DE32245
http://rapidshare.de/files/32773222/Darstellung_der_Acetondi...


Acetone dicarboxylic acid from treating citric acid with KMnO4/H2SO4:
C. R. Hebd. Seances Acad. Sci. 130 (1900) 32
http://rapidshare.de/files/32773009/sur_l_oxydation_manganiq...

J. Am. Chem. Soc. 55 (1933) 1723
http://rapidshare.de/files/32766922/The_oxidation_of_citric_...

(the bold text is a bug in the board software apparantly?)

[Edited on 11-9-2006 by Vitus_Verdegast]




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Chris The Great
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[*] posted on 11-9-2006 at 10:59


I've heard that cocaine with a 4-fluoro on it is about the same but 60 times stronger. It is also uncontrolled in Canada, as in fact are all cocaine analogs...
I have seen the synthesis of the compound before, but I have not found an actual journal about the effects (one site had a name and a date, not further reference to something someone could actually find). So I can't really say if the above is true but it seems to be decently well known on various clandestine chemistry sites. It's just nobody has the reference!

I also saw an analog that had some extremely high potencies for blocking dopamine reuptake, it replaced the normal methyl ester on the cocaine molecule with a plain propyl group (no ester) and a 4-fluoro aromatic ring also directly bonded to the central tropine ring.

It seems that in any case, 4-fluoro rings are always more potent than the plain compounds.


Now, here is a question- wouldn't blocking dopamine re-uptake always make the user feel great? A lot of analogs have very high strengths for causing dopamine levels to shoot through the roof. However, many don't seem to replace cocaine very well, according to the monkeys who get tested all the time. Couldn't it just be that they are not triggering some other receptor involved in cocaine addiction, and that the drugs themselves ARE abusable but simply don't replace cocaine because they aren't mimicking all of it's effects?

It could be that all of these cocaine analogs that don't replace it for addicts might have great possibilities as recreational compounds, it's just no human ever bothered to snort his research project to see how good it was, and when the monkies wanted their crack back they just decided it had no potential as a recreational compound.
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[*] posted on 11-9-2006 at 13:16


On 4-fluorococaine I managed to locate the following paper:

Journal of Neurochemistry Volume 62 Page 1154 (March 1994)
http://rapidshare.de/files/32780562/4-fluorococaine.pdf.html

from page 7:
"There is evidence that inhibition of DA
reuptake by cocaine is responsible for producing euphoria
and its consequent abuse (Ritz et al., 1987).
The PET results with labeled 4'-fluorococaine imply
that para substitution with fluorine does not alter cocaine's
interaction with its binding sites in the brain.
The in vitro competition experiments supported this
implication, because cocaine and 4'-fluorococaine
had similar affinities for the DA reuptake site. They
also exhibited similar affinities for NE reuptake sites.
However, 4'-fluorococaine was about 100 times more
potent than cocaine at the rat brainstem 5-HT reuptake
site labeled with [3H]paroxetine . This observation,
together with the nearly identical striatal kinetics
oflabeled cocaine and 4'-fluorococaine, confirms that
binding to 5-HT reuptake sites is not important in the
striatal uptake of ["C]cocaine. No increased uptake
of labeled 4'-fluorococaine relative to cocaine was
seen in any regions, including the brainstem and frontal
cortex . Presumably, the small size of the baboon
raphe nuclei (1-2 mm) precluded visualization in a
tomograph with spatial resolution limited to 6 mm.
Frontal cortex contains 5-HT reuptake sites, but their
concentration is lower than that of DA reuptake sites
in the striatum . The affinity of 4'-fluorococaine for
5-HT reuptake sites may be too low, or the dissociation
rate constant too rapid, for visualization of frontal
cortex 5-HT reuptake sites against the background
of nonspecifically bound radiotracer. Our ICSO value
of 7.5 nM (Table 3) corresponds (Cheng and Prusofh
1973) to a K; for 4'-fluorococaine for the 5-HT transporter
of 0.3 nM assuming a KD of20 pM for paroxetine
(Ritz et al., 1990). Tritiated paroxetine does preferentially
label in vivo brain regions relatively rich in
5-HT transporters (Scheffel and Hartig, 1989), perhaps
because its affinity is 15-fold higher than that of
4'-fluorococaine . It also binds to nonserotonergic
sites, however (Biegon and Mathis, 1993)."

(My apologies for the Rosco Bodine-quality of formatting)


In my point of view these tropacocaine analogs seem interesting curiosities. Although not as potent as cocaine, they are (relatively) easier synthesised than cocaine analogs and they are legal here in the Carolingian Empire (cocaine analogs too).




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[*] posted on 29-10-2018 at 05:40


How difficult is it to make a potent analogue using tropine? Im a newbie
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[*] posted on 29-10-2018 at 11:51


Quote: Originally posted by dudabuda  
How difficult is it to make a potent analogue using tropine? Im a newbie

I'm pretty sure drug development is off-limits here; ask somewhere else. I will tell you that a pertinent Google search term is "phenyltropane".




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 29-10-2018 at 12:16


Thanks CNA.

If this thread morphs into spoonfeed requests it will get locked.
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[*] posted on 29-10-2018 at 16:49


" How difficult?"

Possible for some; impossible for others.

Exactly what potent analog are you considering making?

And.... Got a permit?

Some of the folks here do. Some don't.

Some may live in places where they don't need one.
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[*] posted on 18-11-2018 at 16:27


https://pubs.acs.org/doi/abs/10.1021/jm980028%2B?journalCode...

I would recommend the piperidine analogues of cocaine as they're potent and relatively easy to synthesize. Also all of the materials may be obtained legally and with relative ease.
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[*] posted on 18-11-2018 at 17:29


Because no synthetize plain cocaine, very easy.

[edit]
Link removed

[Edited on 19-11-2018 by j_sum1]
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[*] posted on 18-11-2018 at 18:11


Because the resurrection of this thread was on shaky ground from the start,
And because it has turned into spoonfeeding recipes for illicit drugs...
I am closing it down.

For all those interested, I am sure you can search and find procedures to do whatever you want. Just not here.
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