Benzothiophene based drugs

[raybeez]

I just had an interesting chat with Limpet_Chicken about the possibility of benzothiophene based tryptamine analogues (ie with an S on the indole ring instead of NH).

Is the indole amine group integral to the activity of tryptamines? Do these exist? If not, would they theoretically be psychoactive? I also think it would be interesting to see how synthetic neurotransmitters (serotonin, melatonin) would work with this modification.

 

[Black]

i am not sure if they would be psychoactive; the sulfur atom is different enough from the N to make to doubt their activity. but i bet the benzofuran analogues would be. the benzofurn analogue of LSD is something i would love to sample.

 

[fastandbulbous]

I imagine that they'd have some slight activity as divalent sulpur atoms are capable of forming (very) weak hydrogen bonds through the electrons in the outer shells doing something similar to the formation of lone pairs of electrons.

There's a paper somewhere in my computer that actually discusses the benzofuran analogues of the tryptamines and they apparently do have a fair bit of the activity of the active tryptamines (in some cases up to 60% of the indolic compound). What's really weird is that the indene analogues of the tryptamine show some activity as well (where the indolic NH is replaced by a CH2 group) - some up to 25% that of the indole/tryptamine

 

[raybeez]

I was thinking along the lines of something Shulgin says in the TiHKAL entry for 5-MES-DMT:

"Sulfur lies in the very same column of the periodic table as oxygen, in the location directly below it. Therefore there are many similarities as to chemical bonding, making things like thioethers that are true analogues of ether. A sulfur atom between two carbons rather than an oxygen atom. Bit, the polarity, and lipophilicity properties are different and the pharmacology is, of course, different. In the phenethylamine series, as reported in PIHKAL, there can be a considerable increase in potency"

Of course he's talking about MeO being replaced with MeS at the 5'- position in tryptamines, but I thought maybe there might be some applicability here as well (at least someone reporting activity (or lack there of) of benzothiophene compounds in literature)

i am not sure if they would be psychoactive; the sulfur atom is different enough from the N to make to doubt their activity. but i bet the benzofuran analogues would be. the benzofurn analogue of LSD is something i would love to sample.

 

[EN21]

S-dmt

The S-DMT should be equipotent to DMT.
See J.Med.Chem. 1979 / 22(4) p.428ff. Serotonine receptor bindings of tryptamine analogues: Richard Glennon and Peter Gessner.
I attached only the table containing the Ki values.

I hope this helps

 

[raybeez]

Thank you, that's exactly what I was looking for.

So: Would it be reasonable to hypothesize that equivalent S analogues of other tryptamines would also be equipotent to their indole counterparts?

The S-DMT should be equipotent to DMT.
See J.Med.Chem. 1979 / 22(4) p.428ff. Serotonine receptor bindings of tryptamine analogues: Richard Glennon and Peter Gessner.
I attached only the table containing the Ki values.

I hope this helps

 

[EN21]

I suppose so, but don't know for sure.