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 compoundsolo - 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.
"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...Vitus_Verdegast - 11-9-2006 at 10:52
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)
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
(the bold text is a bug in the board software apparantly?)
[Edited on 11-9-2006 by Vitus_Verdegast]Chris The Great - 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.Vitus_Verdegast - 11-9-2006 at 13:16
On 4-fluorococaine I managed to locate the following paper:
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).dudabuda - 29-10-2018 at 05:40
How difficult is it to make a potent analogue using tropine? Im a newbieclearly_not_atara - 29-10-2018 at 11:51
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".j_sum1 - 29-10-2018 at 12:16
Thanks CNA.
If this thread morphs into spoonfeed requests it will get locked.zed - 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. Rxogue - 18-11-2018 at 16:27
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. GrayGhost- - 18-11-2018 at 17:29
Because no synthetize plain cocaine, very easy.
[edit]
Link removed
[Edited on 19-11-2018 by j_sum1]j_sum1 - 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.
