What's the most potent 25-I molecule ?

[MedicinalUser247]

I have idea, but it sounds kind of crazy. Make a 5HT-2a full agonist out of Labetalol.

 

[MedicinalUser247]

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

 

[MedicinalUser247]

https://en.wikipedia.org/wiki/25B-NBOMe

 

[someguyontheinternet]

I have idea, but it sounds kind of crazy. Make a 5HT-2a full agonist out of Labetalol.

How would you do that without losing the affinity for beta

 

[MedicinalUser247]

That. I don't know, but that's a real good question.

 

[MedicinalUser247]

So,... How do you propose designing a non lethal 5-HT2a super agonist ?

 

[someguyontheinternet]

I think it would be a good idea to start by looking at the most selective compounds, one that bind to and activate 5ht2a ONLY

From there, small modifications can be made and tested with molecular dynamics and docking to try and improve binding

 

[Rectify]

I think this would be the most powerful 25I, no?

1-(2,5-dimethoxy-4-iodophenyl)-N-((2-methoxybenzyl))2-aminopropane

 

[MedicinalUser247]

Well imagine that, but with naphthalenes instead of phenyls and then adding methoxys everywhere except for the iodo. Weird thing is that a bromo makes it stronger. You think an iodo would.

 

[someguyontheinternet]

Well imagine that, but with naphthalenes instead of phenyls and then adding methoxys everywhere except for the iodo. Weird thing is that a bromo makes it stronger. You think an iodo would.

Why would you think that iodine would be stronger than bromo

 

[MedicinalUser247]

Because it's the heaviest halogen atom.

 

[someguyontheinternet]

Why does heaviness matter?

 

[MedicinalUser247]

I don't know. I just know that things should just work a certain way.

 

[someguyontheinternet]

Try thinking more about electron distribution. Which is more electronegative, iodine or bromine? If an atom is more electronegative it will draw electrons away from a benzene ring which changes how that ring will interact with a receptor protein. There is no hard and fast rule about whether more or less electron density at a ring will increase or decrease affinity but it rather depends on the target receptor and the active site and how the ligand interacts with it

 

[MedicinalUser247]

You know... if some 43 year old high school drop out manages to create a 5-HT2a super agonist before a scientist does there will be a lot of talk.

 

[someguyontheinternet]

To confirm that you have designed one you need to test it in binding assays

 

[MedicinalUser247]

Well I contacted a pharmaceutical company and left a message.

 

[Liser]

How would you do that without losing the affinity for beta

I am kinda new on all of this but could you explain to me how it would lose the affinity for beta receptors?

 

[3DQSAR]

I was under the impression that Nichols et al discovered both the rigid derivative of 2-CB i.e. TCB-2 is the most potent and would expect TCI-2 to have similar activity unless you are going to allow for the NBOMe derivatives. I'm uncertain if those two modifications increase affinity but it is a known compound.

2CBCB-NBOMe

2CBCB-NBOMe | C19H22BrNO3 | CID 57483909 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

I wouldn't touch it with a barge-poll.

Mescaline and 2CB, maybe, but while those N-substituted derivatives are bad news.

I'm surprised that nobody has gone down the bk-NBOme series as, although less potent, they appear legal in most places and the synthesis if facile. I say legal IF you use a synthesis that doesn't have bk-2CB as an intermediate, which I think is possible.

Actually, I've been told that the 4-iodomethyl is the potent 4 substituent, but it's also an alkylating agent, so I would avoid that unless cancer is your thing. Something I wouldn't consider ethical even for animal studies.

But why specifically the 4-I? There are more interesting compounds as yet untested. The 4-ethynyl isn't well explored.