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I Like to Draw Pictures of Random Molecules

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aced126 said:
The link takes me to the start of the pdf only.
Click to expand...

Wait until it loads. (or just enter "16" in the upper left corner once at the link if your browser has the integrated Firefox html *.pdf reader that this library computer has or similar)

Using RTI-126 as an example, I wonder if protonating the nitrogen at the heterocycle would benefit this interaction at all? Anyone with knowledge on electrostatic interactions care to say their piece?

8GsJd.jpg
 
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You can't chose whether to protonate it or not. The protonated and unprotonated forms of the compound exist in equilibrium, depending on the pH of the medium they're in. Can't really find the pKa of 1,2,4-oxadiazole anywhere, so I don't even know if it'll get protonated at physiological pH at the transporter, but my guess is it will, although the tertiary amine also will be. If this is the case, it'll benefit the most in binding affinity if there's an aspartate residue somewhere nearby and it can form an ionic bridge. If not, positively charged drug residues can still form ion-dipole interactions with any amino acid residues bearing an electronegative residue.
 
Nagelfar said:
Wait until it loads. (or just enter "16" in the upper left corner once at the link if your browser has the integrated Firefox html *.pdf reader that this library computer has or similar)

Using RTI-126 as an example, I wonder if protonating the nitrogen at the heterocycle would benefit this interaction at all? Anyone with knowledge on electrostatic interactions care to say their piece?

8GsJd.jpg
Click to expand...

wow! doubly protonated? only in highly (i mean REALLY highly acidic media that would happen.. something like concentrated oleum ie fuming sulfuric acid yes!. the pKa for the second nitrogen protonation(=N => =NH+ ) is about -8! .. that of the first protonation is about 0.. so unless you immerse the target DAT in fuming sulfuric acid there's no way that molecule will exist along with anything resembling a protein called DAT. the mexican cartel used the method to make bodies disappears (Literally without a trace! ).
 
Dissociatives opioid stims..


canv44as_zpsnkoiecbw.png



Bromadol (opioid)

metabolize into


ca77nvas_zpsn9qjmdwq.png



PCP and pyrovalerone

how to get the plasma conc for both activities right about the same for maximum mu (w'out ODing) and stim/dissociatives?
 
DotChem said:
wow! doubly protonated? only in highly (i mean REALLY highly acidic media that would happen.. something like concentrated oleum ie fuming sulfuric acid yes!. the pKa for the second nitrogen protonation(=N => =NH+ ) is about -8! .. that of the first protonation is about 0.. so unless you immerse the target DAT in fuming sulfuric acid there's no way that molecule will exist along with anything resembling a protein called DAT. the mexican cartel used the method to make bodies disappears (Literally without a trace! ).
Click to expand...

What if you subtract the charge from the oxygen like is done in the common NO2 formula? ;-p
 
Here's my piece of advice coming straight from the heart. :) Go get some organic chemistry textbook with the very basics, start with McMurry or Wade, or even start with Clayden, there are some chapters discussing acid-base theory and conformations, and they're very good to start with. If you want to delve into drug design, you need to have a serious background in organic chemistry. Right now you're literally wasting your time in the library looking in the dark and I'm sure you could spend this time more productively. You can also find a lot of free resources on different levels of difficulty from various universities, however, at the very beginning I guess it's necessary for you to know what to look for, I suppose it's functional groups, acid-base theory, and conformations which you should look into, otherwise there's no point in playing with heterocycles and molecules with multiple functional groups.
 
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Nagelfar said:
What if you subtract the charge from the oxygen like is done in the common NO2 formula? ;-p
Click to expand...
Hello @Nagelfar: But it doesn't work that way: just add or subtract charge on atom whenever you feel like it. There is rationale when you see same molecule depicted sometime with =NH+ or sometime just =N. Really just basic organic chemistry. (acid+base <---> salt + water) . The salt (in the case of imino =NH+ functional group) is a positively charged specie and depending on the pH of the medium in which your molecule is, the rx will go one way or the other depending also of the pKa of your molecule. example: cocaine tertiary amine (pKa~8.8) so at pH7.4 (physiological) there will be 1 molecule free base for 10 protonated (salt form) with (+) charge. Now you put cocaine in the gut (pH~3) then you'll have one neutral uncharged molecule(free base) of cocaine for 100000 charged!..etc
I tend to agree with preceding posts: study basic functional groups including n-oxide, nitro, nitroso, sulfonyl sulfinyl, sulfoxyl...etc(since you like sulfo compounds in your design.;)) group and their chemistries including their acidity/basicity reactivity ..etc. It is a must. Then everything will make sense as far as drug design is concerned.
 
aced126 said:
How do you get the methoxy at that position?
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Good catch aced.. I forget to also "retro" the methoxy.. should be like that:

%5B2-(6-methoxy-1H-indol-1-yl)ethyl%5Dbis(propan-2-yl)amine.png


right? this way the 6-methoxy will occupy the 5-methoxy spot of foxy in the receptor? right?
 
is that what you meant? or do you mean "how to get the methoxy in that position" in term of synthesis?? well you can.. ahem ahem!
 
DotChem said:
is that what you meant? or do you mean "how to get the methoxy in that position" in term of synthesis?? well you can.. ahem ahem!
Click to expand...

I meant exactly that; I know these molecules are purely hypothetical but it'd be nice if they could actually have some potentially real value. Your most recent molecule is interesting
 
Lanicemine is a low-trapping NMDA receptor antagonist. However, with a N-ethyl group it would be fairly close to ephenidine.

N-ethyl-1-Phenyl-2-pyridin-2-ylethanamine.png
 
Many years ago, I tried mephentermine in Goa. You could buy it in vials for injection at the pharmacy, just like ketamine. Once it was crystalized we snorted it, and I swear that it was almost indistinguishable to the "street" amphetamine we get in Europe. It's probably only half as potent as pure amphetamine, but as most amphetamine is cut anyway, it came out the same.

If I was an RC vendor, looking for the next mephedrone analogue, I'd make this:

methmephenterdrone_zpswjcoppyt.png


Mephentermine+Mephedrone = Memephenterdrone

So memephenterdrone might be the most obvious name, even though 4-methyl-mephenterdrone would be more correct, but a bit too long. Imo, best would be to join the two Me's, and just call it Mephenterdrone. It has a nice sound to it.

So to sum it up, I'm guessing it'd be less potent than mephedrone (maybe half the potency) But qualitatively probably identical.

Has this compound been thought of before?
 
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