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1,2-dihydro-1,2-azaborine and other heterocyclic C65xH6 ring psychedelics/stimulants?

Limpet_Chicken

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Does anybody have any idea whether analogs of known psychedelic phenethylamine/amphetamines where the phenyl ring is replaced by a 1,2-dihydro-1,2-azaborine ring would be active? or perhaps other heterocyclic rings such as pyridine, phosphazine etc?
 
Unless you administered them parenterally, right? (Of course that would only get you past liver enzymes... if enzymes in the brain also oxidize it then no dice.)

Good luck finding a bioisostere for phenethylamines, this seems like a very interesting and worthwhile path even if 1,2-dihydro-1,2-azaborine itself doesn't pan out.
 
There's thiopropamine (amphetamine with a thiophene ring replacing benzene). Add a couple methoxy groups at positions 3 and 5, something hydrophobic at 4, and maybe you'd get something interesting, but almost certainly worse (qualitatively and in potency) than the corresponding amphetamine, and not remotely worth the synthetic effort.

A pyridine ring would probably give you something histaminergic.
 
There's thiopropamine (amphetamine with a thiophene ring replacing benzene). Add a couple methoxy groups at positions 3 and 5, something hydrophobic at 4, and maybe you'd get something interesting, but almost certainly worse (qualitatively and in potency) than the corresponding amphetamine, and not remotely worth the synthetic effort.

A pyridine ring would probably give you something histaminergic.

The pyrovalerone homologue has been studied and found to be as disappointing as the simple methamphetamine homologue compared to it's parent. A couple of papers on it are listed by Reaxys but nothing of value. I'm sure the Chinese RC vendors would have thrown them out if they were of commercial value to people selling untested compounds with the implicit reason of consuming them.
 
Methiopropamine? have tried it, and quite honestly, couldn't tell much of a difference between it and meth.

Here's a thought..borazine is stable enough to be prepared (IIRC from diborane and NH3...not exactly the most appetizing prospect, given the nature of diborane. Never had the...'opportunity' of dealing with B2H6, although have with pentaborane, and none of the family are particularly pleasant, AFAIK, but have dealt with worse), and its isoelectronic and isosteric with C6H6; would the phosphorus homolog be sufficiently stable for such purposes?
 
Methiopropamine? have tried it, and quite honestly, couldn't tell much of a difference between it and meth.

Here's a thought..borazine is stable enough to be prepared (IIRC from diborane and NH3...not exactly the most appetizing prospect, given the nature of diborane. Never had the...'opportunity' of dealing with B2H6, although have with pentaborane, and none of the family are particularly pleasant, AFAIK, but have dealt with worse), and its isoelectronic and isosteric with C6H6; would the phosphorus homolog be sufficiently stable for such purposes?

Don't trust wiki too much, borazine is not isoelectronic with benzene, despite having same number of electron.
The distribution of them is very different.

Also, borazine hydrolyses in water.
 
^ yeah, due to the differences in electronegativity, the bonding is different from the perfectly aromatic one is benzene. Also affects bond angles.

@Limpet: phosphorus analogues are lousy at forming aromatic rings. AFAIK its atomic radius is too large to form stable sp2 hybridized orbitals necessary for aromatic rings.
 
Do substituted derivatives also hydrolyze?

Yes, with slower rate but still too significant to be stable in "aqueous environment" like the body. (60-70% )
I don't store borazine(s) in solution with more than 1% of water or it degrade too much
 
I think it must say something that while Si has made it to candidates, it's never ended up in a licensed medicine. Derek Lowe has written a lot of commentary on it which is well worth the read. Well, in truth I think 'In The Pipeline' should be read by all.
 
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