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Furo-Indole (Dragonfly-Tryptamine Hybrid

Morninggloryseed

Morninggloryseed

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These are obviously logical, and I'm sure someone has mentioned them before...but I can't find anything in Pubchem and other data bases.

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Is there any activity known with these?
 

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The oxygen would be in the wrong position, because tryptamines bind differently from phenethylamines.

There was a good picture about the differences between trypt/phen binding, in another thread... let me see if I can find it...

here:

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So as you can see, if you wanted to make a furoindole, the furan ring should connect to the 4,5 positions instead of 5,6.


- on a related note, here's something I've been thinking about:

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morninggloryseed said:
What about the corresponding furoindol-8-yl) (ie.e the furan on the corresponding '4' and '5' where oxygen is at the 4.)
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So you'd have the furan in 4,5 with the oxygen in the 4? Well... who knows what would happen, but I suspect it wouldn't be very active: both 5-methyl-DMT and 4-Meo-DMT were of low activity IIRC, so if anything can be extrapolated from that... then again who knows.

Really, I think a dihydrofuran in 4,5 with the oxygen in the 5 would be the optimal choice here. This way the lone pairs will be in the right position to form a hydrogen bond with the serine residue.

One other thing I've been thinking about is the quinoline analogues of various tryptamines. That is, you replace the indole with a quinoline, and the aminoethyl chain would be para to the aromatic nitrogen... As far as I can tell they should be able to fit in the receptor and bind just as well as the indole counterparts.
 
Since there is only an addition of a carbon, and the location of both the Nitrogen on the quinoline and the ethylamine chain match up how could there be much of a change in effects from plain ol DMT and the quinoline dmt? According to tryp binding profile of 5-MeO-dmt there isn't anything interacting with the indole ring besides the nitrogen. Though I guess because it is a tertiary amine it will effect the binding, therefore changing the effects profile.
 
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According to tryp binding profile of 5-MeO-dmt there isn't anything interacting with the indole ring besides the nitrogen.
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Well there's pi-pi interaction with the benzene part of the indole and a phenylalanine residue... I'm not sure if changing indole to quinoline will hinder or improve this.

And yeah, the lack of the hydrogen on the quinoline's aromatic N might change the binding somehow... But it shouldn't matter because it should act as a H-bond acceptor anyway, right?
 
With respect to the bioisosteric replacement of the indole-core in tryptamines with a naphthalene/quinoline-moiety, you maybe like to have a look at agomelatine. It is an already marketed example for such a bioisosteric replacement, which tells us that in principle it is indeed possible to change indole--->naphthalene. A quinoline should be even more similar to the original. Receptor subtype specifity might change though.

Interesting enough, 4-(2-(dimethylamino)ethyl)quinolin-5-ol (i.e. the quinoline-analogue of psilocin) is not known in the literature. Shouldn't be too difficult to make.

Remember that replacement of the benzene-ring in DMT with a thiophene lead to inactive compounds, although thiophene usually works as bioisosteric substitute for benzene (J Med Chem 1999, 42(6), p.1106).


PEACE! - Murphy


P.S. With reagrd to the opening post, neither 2-(5H-furo[2,3-f]indol-7-yl)-N,N-dimethylethanamine nor 1-(5H-furo[2,3-f]indol-7-yl)propan-2-amine are known in the literature.
 
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^with respect they are not know to scifinder/ beilstein which really isn't the same thing.
given the amount of work done on antimalarials in the 40's and 50's it is almost certain that the compound has been made.
 
If so, then the results were not published in any reasonably reputated journal or book. From a scientific point of view this means that they never existed. I couldn't even find a single mentioning in the patent literature.

I understand what you said, but I'm afraid that for practical reasons, one can consider anything that does not show up on SciFinder or Beilstein Reaxxys as "unknown". Results that remain hidden in the file collections of pharma company are of no public importance.

- Murphy
 
I had also thought about this one, but thought the others were sexier. No accounting for taste on my part, this is the most likely winner. How long now till we see it for sale. :)

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^ I'd rather see the one with the non-aromatic furan substitution. Think about the difference between FLY and DFLY compounds, the FLY compounds are far less sketchy...
 
MurphyClox said:
With respect to the bioisosteric replacement of the indole-core in tryptamines with a naphthalene/quinoline-moiety, you maybe like to have a look at agomelatine. It is an already marketed example for such a bioisosteric replacement, which tells us that in principle it is indeed possible to change indole--->naphthalene. A quinoline should be even more similar to the original. Receptor subtype specifity might change though.
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Agomelatine was the one that gave me the idea, actually ;)

I just thought quinoline would be better than naphtalene, for the h-bonding...
 
Agomelatin, hmm, I'm thinking on the G compounds now (particularly 2C-G-N), they're active and could serve as a starting point to move the substituents around respectively remove them one at atime. Just a brainstorming for a potential fruitful new research bone...
 
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