I Like to Draw Pictures of Random Molecules

[Dresden]

I took a semester of German in college and liked it. I also have a thing for German engineered cars. And I'm a big fan of the trance duo, "Gabriel and Dresden." And I read the chapter in pihkal by the same name which described the German city as being one of he most beautiful in Europe until it and its innocent civilians were brutally firebombed by the US; thus the name was meant to critique the atrocity that is modern warfare. Finally, Dresden is the German equivalent of my real first name, Andrew. Both are derived from the Greek, andros, meaning man or strong. Hope that helps.

 

[pharmakos]

you ever read Slaughterhouse Five, the novel by Kurt Vonnegut Jr. that uses the fire bombing of Dresden as a central event/location?

partially based on Vonnegut's real-life experience being a POW during the fire bombings. but it gets away from being autobiographical pretty quickly when they start travelling through time and space and whatnot. =p

 

[Nagelfar]

 

[Dresden]

pharmakos,

I bought that book once, but I never read it.

 

[Dresden]

ICE (IndolylCyclohexylEthylamine)

 

[Dresden]

ICP (IndolylCyclohexylPiperidine)

ICP also stands for inductively coupled plasma and insane clown posse.

 

[Dresden]

ICE also obviously stands for recrystallized:

Or frozen water. Can everybody tell I'm on an indole kick?

 

[Dresden]

iso-AMT

 

[roi]

Fentanyl/Moramide hybrid thingy

 

[Solipsis]

psy daydreams

 

[Raihiar]

Inspired by pregabalin

I think this hasn't gotten the attention it needs.

In my experience PGA needed an awfully long time to start working (in the 2hr. ballpark). Additionally i remember that GHB-Blood-levels do rise faster when consuming GBL instead of GHB (gets absorbed better and the ring-opening takes place very fast in the body.

So is it legitimate to assume the cyclised Pregabalin would be absorbed faster than the open version?
and can i even extend that theory to cylclised Gabapentin?

 

[Solipsis]

I think this hasn't gotten the attention it needs.

In my experience PGA needed an awfully long time to start working (in the 2hr. ballpark). Additionally i remember that GHB-Blood-levels do rise faster when consuming GBL instead of GHB (gets absorbed better and the ring-opening takes place very fast in the body.

So is it legitimate to assume the cyclised Pregabalin would be absorbed faster than the open version?
and can i even extend that theory to cylclised Gabapentin?

Not necessarily: gabapentinoids are tricky bastards to get absorbed well, because they rely on amino acid transporters. Cyclized versions are not candidates for that I think, but OTOH you lose some polarity so it might be absorbed by more 'typical' ways.

Also I think that the correct condensed version would be the gamma lactam:

Cyclizing gabapentin would yield the beautiful spiro:

2-azaspiro[4.5]decan-3-one

(4S)-4-(2-methylpropyl)pyrrolidin-2-one

Anyway if lactams are metabolized in plasma as readily as lactones (within minutes even), the absorption is a non-issue anyway since it would be very effective pro-drugs i.e. having near parent drug properties.

 

[Soulfake]

 

[adder]

psy daydreams

A while ago I had an idea based on 4,5-MDO-DMT. 4,5-MDO-DiPT entry in TiHKAL has a very laconic description of effects, but somehow encouraging, 4,5-MDO-DMT should be active as well with the right ROA, so why not try these & various analogues with different alkyl substituents on the amine:

According to this article 4,5-MDO-DMT is presumably quite similar in potency to 5-MeO-DMT and 4,5-MDO-DiPT is substantially more potent than 4,5-MDO-DMT, so perhaps we're also dealing with qualitative change in effects vs. regular N,N-dialkyltryptamines.

 

[Solipsis]

Cool This whole thread started with the epic wild spotted methylenedioxy fandom..

I briefly considered the above substitutions, but 4-MeO trypt doesn't really bode well for it? But who knows, borrowing from ramelteon is possibly a big mistake since MT receptors are a completely different target, I don't actually know what the tolerance is for 6 and 7 pos substitutions for trypt when you make a structure increasingly PEA-like, and I've got big questions about the 5-HT2a pharmacophore anyway, and the different approaches of trypts and PEAs...:

In my above post I tried keeping the lysergic structure / perspective imaginable.. In LSD and tryptamines a tertiary amine is pretty much essential for major activity (I say major cause obviously there are exceptions that are not inactive), but with the PEA approach suddenly that same amine must be primary?? Making it secondary doesn't do the psy activity good at all, is suggested by the data.

Is there a way trypts are shoved into the receptor considerably deeper or more shallow compared to PEAs changing the pharmacophore SAR rules? Or would we see some interesting things when some PEA amines are made tertiary and *some* trypt amines are made primary? (! AMT) - Could be a matter of weakness to MAO then, but if so what makes 2C PEAs active?

Not sure how much of this territory I am asking about is known, but for 'hybridized' structures to be fancied, insight into the matter must be resolved?

 

[crmt28]

"Extended" arylcylcohexylamines, remind me of Ephenidine:

After seeing the 3rd molecule, it itched me to close that ring, resembles MK-801. Plus silly bonus molecule.

A few more, but also changing the position of the amine:

 

[belligerent drunk]

The extended aromaticity over the whole system means the methylene carbon is less electropositive than it normally would be in a normal acetal, and so it is less susceptible to attack by water. Furthermore, if the oxygen lone pairs are involved in aromaticity, they are less likely to get protonated by the acid and so the whole hydrolysis slows down.

You probably would be able to hydrolyse it, but you'd need much harsher conditions than your usual acetal hydrolysis.

I would say the methylene has a bigger partial positive charge in 1,3-benzodioxole, because the electron density of the C-O bond is shifted towards the aromatic ring (the same way phenolic O-H is weaker and H is more positively charged as opposed to aliphatic alcohols). However, acetal hydrolysis in acidic conditions proceeds by protonation of one of the oxygens, not by a nucleophilic attack on the carbon by water. And as you said, the oxygens are less basic because their lone pairs are delocalized into the ring, making it less susceptible to hydrolysis. If acetals were hydrolyzed by nucleophilic attack of water, then acidity would actually hinder their hydrolysis (H3O+ is a very poor nucleophile).

 

[Solipsis]

Benzylcyclohexylamines would be nice

Good overlay with NMDA as well yeah..

The bottom two compounds look more like something in the direction of pipradrols or https://en.wikipedia.org/wiki/Beta-Phenylmethamphetamine or other beta-subbed stimulating drugs that really rev your blood pressure.

Gonna compare DXM with the rest ;p

Wondering about this:

2-[2-(3-hydroxyphenyl)-1-(propan-2-ylamino)ethyl]cyclohexanone

 

[aced126]

Wouldn't the concentration of H3O+ be negligible compared to the concentration of H2O if H2O is the solvent. But yeah, the oxygens being protonated is definitely required to make it into a reasonable leaving group.

 

[belligerent drunk]

Well yeah, of course in mild acidic conditions it would be negligible, but in principle it would decrease, albeit insignificantly.