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well the carbon between the two oxygenes is sp3 hybridized. so how can it be part of an aromatic system?
 
Oh, that is true for the oxygens as well... it's not 'just flat', it's nearly a tetraeder if you consider the lone pairs instead of the hydrogens of the methylene. I say nearly cause the bond angles are probably a little off. But yeah the polycyclic structure itself without its subs is planar but I'm not sure that it has to do with anything here. :)
 
Bagseed said:
well the carbon between the two oxygenes is sp3 hybridized. so how can it be part of an aromatic system?
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I guess it isn't formally aromatic, but there does seem to be some delocalisation of oxygen lone pairs that makes it planar.

There's this study which at first theoretically calculates that the puckered conformation is stable: http://pubs.acs.org/doi/abs/10.1021/jp994354s?journalCode=jpcafh

Then this later study experimentally shows that that the planar conformation is a lower energy conformation than the puckered one: http://www.sciencedirect.com/science/article/pii/S0009261410003830
 
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aced126 said:
There was a thread I posted a while ago which discusses this in depth.

http://bluelight.org/vb/threads/773845-Storage-of-acetals-(eg-MDA)-in-water
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Even if the aromatic ring of benzodioxoles contributes to more stability due to delocalized electrons, that doesn't actually show how well benzodioxoles hold up in an acid. MDX compounds are probably too short a time in the stomach for it to be a serious matter, and it seems from that other reference that its cytochrome enzymes anyway that metabolize the methylenedioxy if the acetal wasn't hemi'd already.

MDX compounds may hold up a bit better in plain water, but I think acetals do fine already. So not quite sure if someone is saying that benzodioxoles are as an exception incredibly stable and we shouldn't consider them in the acetal discussion but that doesn't seem to be true. Or perhaps relatively speaking it is - according to what aced said, or adder somewhere.

Either way, if you must paste potentially unstable moieties in your designed drug, at least be sensible and reinforce it with pi bonds around it.

It seems the would-be amph analogues drawn earlier could be stable 'enough' given the same advantages, again as long as it's active enough to afford loss from our acidic stomachs and bodily enzymes.
 
Solipsis said:
Even if the aromatic ring of benzodioxoles contributes to more stability due to delocalized electrons, that doesn't actually show how well benzodioxoles hold up in an acid. MDX compounds are probably too short a time in the stomach for it to be a serious matter, and it seems from that other reference that its cytochrome enzymes anyway that metabolize the methylenedioxy if the acetal wasn't hemi'd already.

MDX compounds may hold up a bit better in plain water, but I think acetals do fine already. So not quite sure if someone is saying that benzodioxoles are as an exception incredibly stable and we shouldn't consider them in the acetal discussion but that doesn't seem to be true. Or perhaps relatively speaking it is - according to what aced said, or adder somewhere.

Either way, if you must paste potentially unstable moieties in your designed drug, at least be sensible and reinforce it with pi bonds around it.

It seems the would-be amph analogues drawn earlier could be stable 'enough' given the same advantages, again as long as it's active enough to afford loss from our acidic stomachs and bodily enzymes.
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The extended aromaticity over the whole system means the methylene carbon is less electropositive than it normally would be in a normal acetal, and so it is less susceptible to attack by water. Furthermore, if the oxygen lone pairs are involved in aromaticity, they are less likely to get protonated by the acid and so the whole hydrolysis slows down.

You probably would be able to hydrolyse it, but you'd need much harsher conditions than your usual acetal hydrolysis.
 
Adding an amine to a CP synthetic cannabinoid.

N-methyl-3-(2-hydroxy-4-pentylphenyl)piperidine.png
 
roi said:
MA prodrug, similar to Mefenorex

chloro(methyl)(1-phenylpropan-2-yl)amine.png
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Not quite similar as a N-Cl is not the same as chloroalkyl on the N... this one ^ yields hypochlorous acid i.e. bleach, which oxidizes many biocompounds including DNA and the like. Question is perhaps if it is in appreciable quantities but it's not desirable per say..
May react with water in the air to make at least trace amount of meth which is then a legal drug detection hazard?

What about N-fluoromethylamp though? (Rhodium seems to have supported the idea)
 
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Nagelfar said:
Interesting. The cyclopropane on it. Wonder what modification'd be needed to make a dopaminergic instead of an MAOI
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This isn't including biochem but oh well: What scant literature I've come across on it seems to suggest that it does have some DRA activity. There's that unsourced "fact" on wikipedia about it being 1/5 as potent as dexamp, but yeah there's no source for that...

Can someone explain to me how it's also useful for psychotic depression yet it's such a stimulating compound? Seems like one of many psychiatric inconsistencies.

Also it probably is obvious but it should be useful for ADHD too, considering MAOI-B activity in terms of direct cognition enhancement and MAOI-A activity to deal with impaired cognition as a result of depression.

It really doesn't make sense to continue the war against MAOIs.
 
Neither does it make much sense to continue the war against chlorinated amphetamines such as SHIVA:

1-(3,4,5-trichlorophenyl)-2-aminopropane.png
 
hey Dresden where did you get that your username from? you don't look like you're German...
 
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