3,4-methylenedioxy-1-cyclohexyl-2-methyaminopropane??

[dogtoy]

1-(3,4-methylenedioxycyclohexyl)-2-methylaminopropane better naming -thx

The above chemical would be a cyclohexane version of MDMA. Shorter name 3,4-methylenedioxy-propylhexedrine, if you will. Maybe call it MDPH. Has this chemical ever been proposed, discussed, synthesized, or tasted??

I would imagine the task of building a methylenedioxy ring onto a boat or a chair shape would be very difficult. My thoughts are that if synthesis is possible then it may have some mdma qualities, in much the way that propylhexedrine approximates some of methamphetamine's qualities.

Would it be possible to create the 3,4-methylenedioxy with a cyclohexadiene form (as from hexatriene). Why is every drawing of Propylhexedrine that I can find represented as planar (like benzene)? There are no double bonds as it is cyclohexane, therefore not planar, and chair or boat shaped (planar cyclohexane would be the highest energy state possible). Am I wrong or is every structural representation i've seen of this chemical.

Maybe the loss of potency would be so great as to not be usable. Propylhexedrine is a far less potent than than methamphetamine. Could it be that the dosage needed of 'MDPH' for entactogenic experience would be so high that the body load or peripheral effects would be too much for a person to take?

Would it be possible then to set about making cyclohexyl versions of all PEA (phenethylamines) creating new CEAs (cyclohexethylamines). I would imagine that all of these would have much reduced potency if they indeed had any, but might this not be a good way to circumnavigate analogue laws? because anyone with a background in chemistry can tell you that the shape of cyclohexane is nothing like a phenyl ring, possibly making the analogue argument a bust.

I'm sure there are issues which i am not taking into much account about how unstable the structural shape of cyclohexane is compared to benzene. Maybe one day i'll do all this and write the CIHKAL. If cyclohexane was used there would be some wild looking 3d structures.

Does anyone have any info about propylhexedrine trials or studies? Any info on binding affinities and such? I would really like see data about how propylhexedrine compares to methamphetamine. Anything from adrenergenic activity to release of DA, NE, and SERT.

And now, please tell me what you think.

thanks
-DT

 

[dogtoy]

*edit* had really bad structural representations here. better ones below

 

[Smyth]

No, the aromatic electrons are needed.

 

[dogtoy]

OK...here are some better structural representations. Semi 3d so better idea of shape than before. If people have structural modeling software pm me and I can send full 3d models.

Also I have put the IUPAC names for these chemicals in it.

I don't really understand why you would say that the aromatic electrons are needed...propylhexedrine definitely has some activity.

 

[Smyth]

This is the first I have heard of propylhexedrine.

 

[Coolio]

I've read a bunch of reports of propylhexedrine IV being similar to amphetamine/methamphetamine IV. There's a journal article about deaths in Dallas resulting from chronic propylhexedrine injections. In another journal article propylhexedrine substituted for amphetamine in two of three pigeons tested, while phenylpropanolamine didn't. http://jpet.aspetjournals.org/cgi/content/abstract/241/3/817

 

[fastandbulbous]

The name you want is:

1-(3,4-methylenedioxycyclohexyl)-2-methylaminopropane

Not a clue if it would be active, but I wouldn't hold my breath, as being able to cause dopamine and serotonin efflux is a very particular business; it's why IAP isn't like MDA, or 4-methyl-3-methoxyamphetamine, or even 5,6-methylenedioxy-2-aminoindan. They either tend to act on either dopamine or serotonin, but not both. The flat 5-membered ring is integral to serotonin activity, but the oxygen at the 3-position seems to be needed in order to have an equivalent effect on dopamine. Cyclohexane isn't flat (planar) like a benzene ring (it forms either a boat or chair configuration), so you're not going to get a planar 5 membered ring.

The best bet for something comparable to MDMA is

6-(2-methylaminopropyl)-2,3-dihydrobenzofuran.

I'll do a structural diagram, if wanted, after I've made food, cleaned cat litters etc

 

[Smyth]

Or even just 2-napthyl-isopropylamine. Although this wont necessarily be fun, it certainly appears to circumvent the analog act. 2-Napthaldehyde is commercially available also if anybody is interested. In fact so is nicotinaldehyde for that matter..

 

[fastandbulbous]

2-napthyl-isopropylamine isn't like MDA in action, it's just a plain stimulant (and not a very good one at that). I thought it might be a promising amphetamine replacement, but someone at the hive (who'd synthed some) said it wasn't up to much - about on a par with phentermine.

I've attached a jpeg with the structure of the methylenedioxy analogue that's most like MDA (fig 1a); there's always hope that the N-methylated version would also be like MDMA (fig 1b). According to Dave Nichols, 1a has a profile not far removed from MDA in terms of 5HT & DA.

Theres also diagrams of the boat/chair conformations of cyclohexane - you can see that attaching a 5 membered ring isn't going to be anything like the same sort of shaped molecule as seen with MDMA, and conformational shape is one of the really inportant featres when it comes to receptor binding (whether it be to cause efflux, inhibit reuptake or act as an agonist/antagonist)

 

[dogtoy]

Yeah I got that about the boat and the chair, that's why my original drawing looked like the 2d versions of those. The second set of drawings I did was supposed to be a more "3d" representation of the boat/chair thing. At least that's the best angle I could get the ChemSketch 3D wireframe.

Here's the original bad 2d drawings if you want to see them.

Honestly I was just wondering if this might deserve some research. If you render these if full 3d, they do look very much like the proper amphetamines straight on, but rotate it a bit and it's obviously a rollercoaster like shape to say the least. I would understand everyone just poopoo-ing the idea right out, if it wasn't for the fact that I know propylhexedrine has amphetamine-like effects.

 

[fastandbulbous]

Yes, but N-propylamphetamine has an amphetaminelike profile of action (only it requires twice the dosage), but N-propyl MDA is inactive according to Shulgin. Theres a paper about indane and tetralin analogues of MDMA/MDA and that's where the data about the SAR came from, as any MDMA analogue would need to have a comparable effect on the 5HT and dopaminergic (and possibly noradrenergic) systems. The main pharmacological effects of stimulants like amphetamine are mediated via dopaminergic and noradrenergic systems alone (methamphetamine does have some serotonogic effects, but they're not responsible for the main pharmacological actions - although it might play a role in the neurotoxicity of meth)

 

[Grignard]

Hmm, something that is interesting about the cyclohexane MDMA/MDA analogue would be the introduction of three new stereocenters. It would be interesting to perhaps put the various enantiomers and diastereomers into a good molecular modeling/comp chemistry package and see if it can spit out the projected most stable conformation of each isomer and the energy differences between them.