Iodide-DragonFLY

[MedicinalUser247]

I just wanted to hear your opinions on Iodide-DragonFLY. Its supposed to be a very potent 5-ht2a agonist, but I don't think I'd ever want to try it. What are your thoughts on Iodide-DragonFLY ?

 

[Skorpio]

I wouldn't even want to try bromo dragonfly. That sounds almost as bad as TFM dragonfly.

I wish efficacies at receptors were recorded more often in studies, or these days g protein/beta arrestin efficacies. Receptor affinity doesn't always paint the whole picture, with regards to the strength of a drug.

 

[MedicinalUser247]

What do you think is stronger ? Iodide-DragonFLY or LSD ?

 

[Skorpio]

Bromo dragonfly seems to have a near-tenfold lower affinity than DOIfor 5HT2A in this study, and in this study shows that LSD needs a 7 fold higher concentration than DOI to displace radiolabeled DOI from receptors. It also shows DOI having a lower affinity than DOB, which gives credence to your hypothesis that iodo dragonfly would be more potent.

Because the assays in each paper differ quite a bit, I am hesitant to actually quantify how much stronger bromo dragonfly is than LSD, but because it is stronger than DOI, which is stronger than LSD, I think it is safe to assume that it is stronger.

Edit: none of these studies talked about efficacy/side effect profile. Based on the 25x series and the dragonfly series causing lethal overdoses versus LSD, I do believe they have more efficicacy at the 5HT2A receptor than LSD does (which is known to be a partial agonist).

 

[AlsoTapered]

The deaths associated with this class are a concern. Skorpio is quite right - affinity ≠ efficacy. The term 'associated' is used in nearly all reports. One guy drowned in his own vomit... what is going on with a 5HT2b ligand causing such symptoms.

 

[sekio]

Iodo-DragonFLY would be a "tool compound" at best, but there are already better high affinity 5HT2a ligands around.

 

[AlsoTapered]

Iodo-DragonFLY would be a "tool compound" at best, but there are already better high affinity 5HT2a ligands around.

We made 2CI in The Netherlands because while 2CB & 2CC were banned.... 2CI was not.

 

[sekio]

Cool fact, but not really relevant to the topic at hand.

It appears that Dave Nichols has only ever made bromo-DragonFLY. Looking at the synthesis, it would not be terribly hard to substitute I₂ for the Br₂ used to install the halogen. (Or, alternatively, some sort of chlorinating/fluorinating/trifluoromethylating agent for the respective analogues.) Alkyl analogues would probably need different synthetic methods.

For those who really want to know: The synthesis actually begins with DOH-FLY (1-(2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)propan-2-amine, SMILES: CC(N)CC1=C2C(OCC2)=CC3=C1OCC3 ), the nitrogen is protected (as a trifluoroacetate), then it is brominated with Br₂ (forming N-TFA-DOB-FLY), the "wings" are oxidised with DDQ (forming N-TFA-Bromo-DragonFLY), and finally the nitrogen deprotected with base forming Bromo-DragonFLY as a freebase, which was added to ethanolic HCl and diluted with ether, forming the final product: Bromo-DragonFLY HCl.

If you just avoid the DDQ you could make much safer and less superpotent analogues. (Bromo-DragonFLY is a MAOI as well as a 5HT2A agonist)

 

[AlsoTapered]

The key takeaway from the fly/dragonfly series is that the 3 rings should be planer (which is why the double-bonds are added) and why 5/6 APB are more potent than 5/6 (M)APB are more potent than 5/6-(M)APDP.

I did wonder about placing an S in place of the O in the 6 series (where it's in the meta position and so not an MAOI. We may yet see it but given the difficulty the Chinese had making the examples with an O (positional isomers was a perennial problem and why the succinate replaced the hydrochloride (the impure product wouldn't form the hydrochloride salt), I'm not holding my breathe.

But in the spirit of enquiry, and knowing Shulgin produced 4T-MMDA-2 (which seemed active), has anyone considered this second possible series of MDMA-like compound that replaces that single O with an S.

 

[sekio]

(reading the PiHKAL entry for 4T-MMDA-2) "1.3 g 5-methoxy-6-(2-nitro-1-propenyl)-1,3-benzoxathiol as San Francisco Giants-orange-colored crystals."
I love Shulgin's writing.

I can find no reference to either benzo[d][1,3]oxathiole-6-carbaldehyde or 6-bromo-benzo[d][1,3]oxathiole (likely 4T-MDMA precursors). Benzo[d][1,3]oxathiole is known though.
I guess nobody has gone down that road? I wonder why Shulgin made the 4-MeO compound and not 4T-MDA/MDMA ... could it be they're a bastard to make or the usual reactions don't work?
2-mercaptophenol is available from Aldrich for CA$100/g, for those willing to take a crack at it.

Also, the sulfur would provide an additional metabolic handle (could be oxidised to the sulfoxide and then sulfone).

Now, how about selenium?

 

[AlsoTapered]

Sure, S can be oxidized but I have never seen it occur in an aromatic system (not that I can claim to have seen many).

Selenium - I REALLY don't know. Ask Rectify, I'm sure (s)he knows.

 

[sekio]

> I have never seen it occur in an aromatic system
Well, first off, the dioxole ring ain't aromatic.
And you mean to tell me you forgot about Dre thiophene?

Isoelectronic with benzene. Hence, tiletamine, methiopropamine, etc.

> Selenium - I REALLY don't know. Ask Rectify, I'm sure (s)he knows.
How about I give him a full moon? Given that selenium is named after that...

 

[AlsoTapered]

I was about to say 'I used to go out with a girl called Selene' but then I thought that truthfully, she invited me over for meals several times... and for SOME reason she preferred to serve them in her bed. I was about 25, an age when guys are supposed to think that it's the PERFECT setup - but I was rapidly losing self-respect. She was quite the looker but MAD and, as it tuned out, screwed just about every man she knew. To be fair, she didn't split up couples...

But you missed a trick, sekio, move 1 square left on the periodic table and make your 5-membered unsaturated ring. You got me?;-)NOW we are cookin'!