I Like to Draw Pictures of Random Molecules

[sekio]

Why so?

no/very little steric hindrance around the two outer carbons (if you count from the top as #1 they are the 3rd and 4th members of the ring)

look up the mechanism of acetal hydrolysis

also enzymes in biological systems can catalyse this rxn just as well as H+, presumably also certain metals/ions, etc

you are right that the ethylene glycol generated wouldnt be toxic but the hydrolysis of the ring would destroy the activity

a better analog for the ester group (die Ester-Gruppen??) would be an oxazoline or whatever is present in that one RTI compound - a ring just like that acetal except with a nitrogen with a double bond in it present in the place of one of the oxygens

 

[Pomzazed]

Why so? Cyclic acetals are more stable than normal acetals and anyway doesn't acetal hydrolysis occur slowly unless catalysed by H+. By the same argument you could say that methylphenidate will rapidly hydrolyse to ritalinic acid and methanol (which might blind you...not, not at that dose anyway). Ethylene glycol is not toxic in milligram rangeff.

1.well, I retract the kidney stone i said above then, I forget about the dosage range which is small, even a gram of that hydrolyse to only milligrams range, so you are right on this part.

2.I still stand about hydrolysis. It is tru that the oxazolidine is stable in neutral and basic media, but in biological environment, if you eat it, with pH 2 in the stomach, it breaks to aldehyde and MEG rapidly, even when smoked/evaporate/snorted or injected, there are several enzymes in bloodstream that catalyse the breakdown of this acetal. The rate will be diminished by steric hindrance of carbon4,5, which in this case is no steric at all (all 4 substituents there are H's)

3. Ester is harder to hydrolyse than (aliphatic) cyclic acetals. Thats why acetals are often used as protecting group in org syn.

4. I do not say that acetals can be used in bioactive compounds, yes there are several, for example: topical steroidal drug: Triamnicolone Acetonide. But this wont hydrolyse so easily, look at how C4 and C5 steric demands are.

better analog for the ester group (die Ester-Gruppen??) would be an oxazoline or whatever

Oxazoline would be much more stable and mimics ester better with that p-orbital.
Exchange MEG to MEA and additional dehydrating base and you form oxazolidine from aldehyde, then You can make it from oxazolidine to oxazoline by [snip]No synthesis discussion[/snip]
(*hint: strong halogenated oxidizer)

 

[crmt28]

A little more info on the last compound I posted. It may have lot of potential!

Let's look at F (pretty unknown compound buried in PiHKAL):

It's 15x less potent than DOM, but it was never tested. Probably active near 70mg or so.
Then we have F-2 and F-22, which add methyl groups on the 2 position of the furan ring, and are noticeably weaker. (40x weaker than DOM)

Shulgin was planning to try F-3 and the benzopyran analogues, but he gave up due to the hard synthesis and loads of chiral centers.
This seems to be a much better idea, since it's basically extending the chain on the 4-position. Real shame he gave up.

Here are some more compounds expanding on that:

F-(2-HemiFLY) - Adding a HemiFLY structure to F. This one could probably be very close to DOM in activity by weight.

F-3-(2-HemiFLY) - Changing the 3rd position instead of the 2nd. If this could increase potency (look at the molecule and think of 2C-D vs 2C-E) it would be a winner!

Let's get crazy here with not so serious compounds:

2C-G-4 and 2C-G-5 analogues:

Bonus semi-related compound:

3-Me-6-APB (3-methyl-6-(2-aminopropyl)benzofuran)

 

[Incunabula]

Nice molecules, crmt28. Your 2C-G-4 and 2C-G-5 analogues looks a little too bulky, but they are very interesting.

They remind me a bit of some molecules I drew a year ago or so. They are kind of a mix-up of the fly's and indanes (Like 2CB-ind or Jimscaline) I think there's a they could potentially be active according to the psychedelic phenethylamine SAR we know. If there is a way to synth them, that is.

I like the symmetry.

 

[aced126]

3-methyl on the furan ring might cause too much steric hindrance. SERT is tight. A methyl group on the methylene carbon of MDMA (ethylidenedioxymethamphetamine) halves potency. 2 methyl groups (isopropylideneMA) and activity is abolished.

 

[DotChem]

Valeroxamine ...

what you guys think about these?? MXE open-chain

 

[pharmakos]

almost looks like gabapentin or pregabalin when you open it up

gabapentin

pregabalin

 

[Nagelfar]

Spoiler: Cruft you don't need to see

Don't you dare say it's fatuitous ;-p

"Cleaned up":

*You* clicked on it.

Stimulant?

 

[crmt28]

^ Looks like a Harmaline/Phenethylamine hybrid!

"Closer" versions:

 

[Nagelfar]

meta-bromo-(2-methyl-2-butanol)-naphthidate (would that still be "meta" on a naphthyl or is the nomenclature different?)

Perhaps simplify it as thus:

Should have good affinity unless one 3'/meta position need be free for optimized binding.

For curiosities sake:

From a doodle at my out-patient group:

 

[Nagelfar]

^ Looks like a Harmaline/Phenethylamine hybrid!

"Closer" versions:

Speakin' o' hybrids check this one out, epiphany inspired just moments ago:

Amylocaine (the very first synthetic topical anesthetic based on cocaine, residual stimulant properties?) + dimethylaminopivalophenone (simplest opioid)

Simplest uni/mono-molecular speedball?

EDIT: I can get it even closer; containing all the constituents of both (OK, minus an oxygen), if I just make it the salt:

 

[Solipsis]

Oh awesome, after PV type stuff finally another stim that promises to reek of semen ;p

 

[DotChem]

DXM ..

Open-chain ..

look like Tramadol ???

 

[DotChem]

almost looks like gabapentin or pregabalin when you open it up

gabapentin

pregabalin

Nice observations! also like phenibut.. who knows they might be GABA-ergic altho they're Alfa AA analogs instead of Gamma!

 

[pharmakos]

DXM ..

Open-chain ..

look like Tramadol ???

interesting.

 

[Nagelfar]

Mini-phenyltropane

MPH variant:

 

[Solipsis]

DXM ..

Open-chain ..

look like Tramadol ???

Sure, cause the clarifying comparison would be not with DXM but with the other stereoisomer of methorphan:

https://en.wikipedia.org/wiki/Levomethorphan

An opioid roughly as potent as hydrocodone.

 

[aced126]

Speakin' o' hybrids check this one out, epiphany inspired just moments ago:

Amylocaine (the very first synthetic topical anesthetic based on cocaine, residual stimulant properties?) + dimethylaminopivalophenone (simplest opioid)

Simplest uni/mono-molecular speedball?

EDIT: I can get it even closer; containing all the constituents of both (OK, minus an oxygen), if I just make it the salt:

Charged species won't cross BBB.

 

[roi]

 

[DotChem]

Sure, cause the clarifying comparison would be not with DXM but with the other stereoisomer of methorphan:
https://en.wikipedia.org/wiki/Levomethorphan
An opioid roughly as potent as hydrocodone.

You're right! I drew the "wrong" stereoisomer or shall we call it the "opioid-like stereoisomer" around the C -Ph carbon?

Yes the Cis (that is the 3MeOPhe and CH2NHCH3 in cis, Zusammen in German) overlay with dextro-metorphan (DXM) like this:

----->DXM-like dissociative



and the (+/-) trans with levo-metorphan and (+/-)tramadol..

"Cis-Tramadol"
--->Levomethorphan-like opioid ..

so in theory then "cis" Tramadol should have dissociative but not opioid .. would be an interesting RC if it is easily accessible synthesis-wise! (from tramadol I guess it should be possible... ) "pure" DXM-like dissociative with no opioid to worry about! may be some stim?? but pretty safe I would imagine!