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2,5-dimethoxybenzyl Bomamine analogs

H

hjalmar

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Mar 31, 2010
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I was wondering if anything is known about the bomamine analogs of phenethylamines obtained from reductive amination of the 2C-X phenethylamines with 2,5-dimethoxybenzaldehyde?

Have N-(2',5'-dimethoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine and similar compounds been tasted yet?

I can't seem to find anything on their activity using google.
 
I thought there would be a good chance that someone already tried this, as the bomamines have been known for some years now and the 2,5-dimethoxy substitution pattern holds some merit compared to the 2-methoxyphenyl ring, in the sense of fitting the receptor and the specific hydrogen bonding. As the 2C-X compounds are most commonly produced from 2,5-dimethoxybenzaldehyde, one would think that someone already had that idea. Oh well, I might look into this during the summer.
 
hjalmar said:
the 2,5-dimethoxy substitution pattern holds some merit compared to the 2-methoxyphenyl ring, in the sense of fitting the receptor and the specific hydrogen bonding.
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Yeah for the phenethylamine part, the N-benzyl bit binds in a different region of the receptor though, and there's not necessarily any room or H-bond donor there for a 5'-MeO.
 
I think the 4-MeO homologue was tried and was less active, but I can't remember the data completely.
 
Yeah, I remember seeing 2,4-dimethoxybenzyl-2C-B being about 10 fold lower in affinity than 25I-NBOMe and 2,5-dimethoxybenzyl slightly lower than that. It was on a postersession a while back.
 
As i mentioned this was at a postersession a year back or so (ACS I think), but a little digging came up with this page where there are several interesting PhD-theses. The last link on the page is the one you want to take a look at.
 
Wow thanks, how did we all miss that one! Compound 4.7 is one of the most exciting structures I've come across in a long time :)
 
trans-4.7 is very interesting, but not one we're likely to see anytime soon.. 25CN-NBOH looks simpler but I have a feeling that NBOH's won't work well in vivo because of metabolism by glucuronidation of the free phenol.
 
Cortexiphan said:
trans-4.7 is very interesting, but not one we're likely to see anytime soon.. 25CN-NBOH looks simpler but I have a feeling that NBOH's won't work well in vivo because of metabolism by glucuronidation of the free phenol.
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Actually, the 25X-NBOH's are quite active, but for some reason have not made much of an appearance. 25B-NBOH is active sublingually or nasally at 300-400 ug, comparable to 25B-NBOMe. However, it has rather different pharmacokinetics, with a short peak of about 1 hour, then a quick dropoff to baseline in 1-2 hours. Total time, 3-4 hours, about half that of the NBOMe. This suggests more rapid metabolism, possibly due to glucuronidation, as you suggest. However, the pharmacokinetics of the NB's (no substituent on the benzyl) is very similar to NBOH's, and they are not substrates for glucuronidation. The NB's are also weaker, with activity at 6-12 mg.
 
tryp2fun said:
Actually, the 25X-NBOH's are quite active, but for some reason have not made much of an appearance. 25B-NBOH is active sublingually or nasally at 300-400 ug, comparable to 25B-NBOMe. However, it has rather different pharmacokinetics, with a short peak of about 1 hour, then a quick dropoff to baseline in 1-2 hours. Total time, 3-4 hours, about half that of the NBOMe. This suggests more rapid metabolism, possibly due to glucuronidation, as you suggest. However, the pharmacokinetics of the NB's (no substituent on the benzyl) is very similar to NBOH's, and they are not substrates for glucuronidation. The NB's are also weaker, with activity at 6-12 mg.
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That sounds pretty ideal -- the long half-lives of the NBOMe drugs and most other psychedelics make them fairly difficult for people who work all the time.

That the ether and the free alcohol have similar activity though is a little curious to me; I guess the oxygen is just there to have its lone pair electrons interact with a hydrogen somewhere in the vicinity. If this were the case, would the aniline homologues also be active?
 
From what I can tell, there is no data on aniline derivatives. I suppose this principle could also be applied to the methoxy-groups in the 2 and 5 positions of the phenethylamine, but I can't remember having seen such analogues either. Maybe there is something about anilines that's just off?
 
Cortexiphan said:
From what I can tell, there is no data on aniline derivatives. I suppose this principle could also be applied to the methoxy-groups in the 2 and 5 positions of the phenethylamine, but I can't remember having seen such analogues either. Maybe there is something about anilines that's just off?
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The NBOHs bind to the 5HT-2a receptor in vitro as good as or better than the NBOMes. Normally, one would not expect the phenolic compounds to get across the blood-brain barrier very well, since they are pretty polar and hydrophilic. The obvious exception is the 4-OH-tryptamines, which Shulgin suggests form an intramolecular hydrogen bond with the tertiary amine. Similarly, I think the NBOHs can form an intramolecular hydrogen bond with the 2-OH of the benzyl and the secondary amine, that lets them get across the BBB. However, there was a paper by Nichols (I think) that suggested that the 2-OH form of DOM was still active.
 
tryp2fun said:
The NBOHs bind to the 5HT-2a receptor in vitro as good as or better than the NBOMes. Normally, one would not expect the phenolic compounds to get across the blood-brain barrier very well, since they are pretty polar and hydrophilic. The obvious exception is the 4-OH-tryptamines, which Shulgin suggests form an intramolecular hydrogen bond with the tertiary amine. Similarly, I think the NBOHs can form an intramolecular hydrogen bond with the 2-OH of the benzyl and the secondary amine, that lets them get across the BBB. However, there was a paper by Nichols (I think) that suggested that the 2-OH form of DOM was still active.
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I was actually thinking about anilines (dimethyl?, monomethyl?) in the 2- and 5-position of the phenethylamine, not phenols.
 
Something like this

2h66fyv.jpg
 
Cortexiphan said:
Something like this

2h66fyv.jpg
Click to expand...

Man, those look toxic as hell. 8o p-Phenylenediamines undergo redox cycling reactions with molecular oxygen to generate superoxide, peroxide and peroxy radicals. It essentially the same thing that MPTP does to cause Parkinson's.
 
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