I Like to Draw Pictures of Random Molecules

[Nagelfar]

Yeah alright then, the carbomethoxy might not be essential. However compare methylphenidate to its counterpart with a saturated beta carbon (I drew it a while ago, was apparently an already documented releasing agent which caused seizures at low doses). The removal of the carbomethoxy group confers releasing qualities.

Perhaps in some occasions but 4'-NO2-phenyltropane (non-ecgonine i.e. sans the carbmethoxy) seems to have been vouched for as not emulating the stimulation conducive to observing phosphorylation compromised life-cycle of MAT (quickly flushed from BBB i.e. cocaine comparable duration)

 

[Midnight Sun]

Yeah good idea Midnight, presuming the molecule pharmacodynamics aren't significantly altered due to the new moiety.

I'm sure it would still fit in the binding pocket however the obvious metabolic result concerns me: would it be, let's say, 5 hours of tripping then a sharp dropoff to residual stimulation that won't dissipate for 20 hours?

I dunno, relocating the acetoxy to the most unimportant position of 3,4,5 TMA (3 I think) might be better

I made this weird sort of hemifly thing:

I'll just stop lol

 

[aced126]

I'd actually say the half life would be similar to methylphenidate (1-2 hours) as both molecules would get hydrolysed at the same rate by the esterase enzymes.

 

[roi]

Phenobarbital/PCP hybrid:

 

[Midnight Sun]

I'd actually say the half life would be similar to methylphenidate (1-2 hours) as both molecules would get hydrolysed at the same rate by the esterase enzymes.

was this directed at me?

if so the metabolite half life itself is what concerns me as it's more than capable of peripheral stimulation for hours...and hours... basically until MAO can deaminate it

***

any bourbon drinkers ITT? someone recommend me something <20$ to drink tonight

 

[aced126]

was this directed at me?

if so the metabolite half life itself is what concerns me as it's more than capable of peripheral stimulation for hours...and hours... basically until MAO can deaminate it

***

any bourbon drinkers ITT? someone recommend me something <20$ to drink tonight

The carboxylic acid metabolite wouldn't cross the BBB much so I don't think peripheral stimulation would occur. And yeah, it should mostly be hydrolysed outside the brain, in the liver.

 

[Dresden]

Note the similarity of ester meth

ESTER METH

to mexedrone, a new 4-MMC substitute research chemical.

MEXEDRONE

I have come to the tentative conclusion that R-(C=O)-OCH3, R-(C=O)CH2CH3, and R-CH2OCH3 are largely bioisosteric. Comparing sufentanil to fentanyl led me to formulate this hypothesis.

 

[aced126]

They are not bioisosteric... they have different chemical properties and thus have different pharmacodynamic and pharmacokinetic effects. Here is a hypothetical situation:

Say your first compound was able to bind to the active site of an enzyme where the ketone formed 2 hydrogen bonds with serine residues and the single bonded oxygen also formed 2 hydrogen bonds with say a tyrosine and threonine residue. Your second compound would only form the first 2 interactions described. Your third molecule would only form the 2 latter interactions described. The first molecule would bind strongly to the enzyme and inhibit it the most. Likewise if R is aromatic there will greatly differing ring density changes. The first 2 compounds will withdraw electron density by conjugation (the first compound doing so more) and the final compound will actually increases electron density (or maybe decrease it slightly, but much less so than the first 2 examples; there are 2 competing factors: the electron pushing effect of the methyl group and the inductive electron pull of the electronegative oxygen. This is going to have effects on pi stacking etc, so again it might change pharmacodynamics at the biological target.

Furthermore, there will be pharmacokinetic differences. The ether will have the longest half life. The ketone can be reduced to an alcohol and conjugated for easy excretion. The first molecule can be cleaved by enzymes to give a very polar and easily excretable carboxylic acid.

If 2 drugs with different structures work, that does not imply the 2 structures are bioisosteric, but rather that both the molecules just fit the pharmacophore. There are different pharmacophores for different biological targets. This may work for opioid receptors or MATs, but you can't generalise that to the vast array of proteins and DNA which exist as biological targets. I'll try dig up some counter examples where your hypothesis is contradicted.

 

[Dresden]

Maybe so, maybe not.

I'm aware they have wildly differing pharmacokinetics.

Actually, a couple of those look too similar to poison hemlock's active ingredient, coniine, for comfort.

CONIINE

Safety testing (not on yourself, either) is again of paramount importance!!!

* * *

In other news,

TRYPTACAINE

 

[Nagelfar]

Actually, a couple of those look too similar to poison hemlock's active ingredient, coniine, for comfort.

CONIINE

Well, you have those coca alkaloids like ferruginine:

Which look like toxins, one named for instance "Very Fast Death Factor" (VFDF):

 

[Nagelfar]

Doxpicomine

8 times morphine.

chemicalize.org has been on the fritz for me lately, I have some compounds I want to draw related to the above, and chemicalize.org keeps giving me a 503 temp service unavail. msg. (and has for the last three days from the library) anybody have any other html online chem programs? I know clubcard told me about one that rendered in 3D also to compare structures and I lost in which post he told me about it. Could someone PM me with a couple of different sites so that I may keep churning out the random molecular madness?)

EDIT: got it to work for a second:

coniine + VFDF ( ;-p )

EDIT:

Really wanted to post this other one but chemicalize.org is going on the fritz again. Did it get too popular for its server to handle or something?

EDIT:

2 minutes left on lib. comp. got this to work:

Peroxides make it unstable? I like how the carbmethoxy shares the 3 position with the benzoyloxy if at the least. V. high electronegativity though. ;-p

 

[aced126]

Just use opsin if you know the nomenclature.

 

[Dresden]

Too many oxygens in too close a vicinity for that last one to happen.

But yeah, opsin or MarvinSketch.

ISONICOTINE

 

[neurotic]

isonicotine, that's a sexy molecule with a sexy name... how different from benzene is pyridine? i.e. could one expect that molecule to behave like amphetamine? please chemistry, please

 

[aced126]

Kinda similar, kinda not...

In pyridine, there is a basic nitrogen with a lone pair in a plane perpendicular to the pi cloud; I'd imagine it could form H bonds with suitable amino acid residues like serine. It could also become protonated and form ionic interactions with negatively charged amino acid residues like aspartate. The electronegative N will withdraw sigma electron density from its nearest surrounding 2 carbons the most but I'm not completely sure what biological effect this could have. Not sure on the effect of possible pi stacking interactions a pyridine will have. I'll do some research and expand this post.

 

[roi]

 

[Nagelfar]

But yeah, opsin or MarvinSketch.

MarvinSketch is chemicalize.org, damn thing still isn't working right.

There was a 3D one clubcard mentioned somewhere, back in this thread I believe, that I can't find now.

opsin:

I found the shotty pubchem one:

caffeicaine

 

[aced126]

Roi, rationale for trifluoroethyl moiety? Why can't it just be a tertbutyl group if you're looking for steric hindrance of carbonyl carbon?

 

[roi]

random != rationale

 

[SKL]

Find mephedrone too short-acting and compulsive? Mephedrone ER, anyone?

Captadrone.

Mephevanse.

(edited to remove some things I realized need a little work...)