I Like to Draw Pictures of Random Molecules

[Nagelfar]

3β-styrene + tricyclic tropane + 2β-isoxazoline w/vinylogous stem

logP: 5.61
Polar surface area: 51.13
Fraction of SP³: 0.39

=

^I just like how it looks, correct me if I'm wrong, but an FSP³ of 0.39 isn't shabby, or am I off-base? (EDIT: just noticed I forgot to put the p-nitro/NO2 on the 3 beta terminating phenyl that I had on my sketch of the above compound)

^Since the IC50 (nM) of cocaine for DA uptake is 209, and the 3β-styrene analog is 5(!), the 3β-carbamoyls have a nitrogen on the bridge, so something azido-esque was my thinking for this one.

 

[Friman1987]

Would you mind using the following code in your post though, if you use such huge images:

[nsfw] IMAGE [/nsfw]

yes, sir


It would be interesting with some new tryptamines.

 

[DotChem]

Aza-DragonFly


and

Buddhanamide

Oh sorry I thought you meant what I would name them.

IUPAC

1-{8-bromo-1H,5H-pyrrolo[2,3-f]indol-4-yl}propan-2-amine

1-{8-bromo-4,10-dithia-6,12-diazatricyclo[7.3.0.0³,7]dodeca-1,3(7),5,8,11-pentaen-2-yl}propan-2-amine

I like Buddhanamide better though even it doesnt have an amide sounds like Anandamide (name coming from Ananda who was the Buddha assiatant and Ananda mean GreatBliss in hindu!)

 

[DotChem]

Try here : http://isciencesearch.com/iss/default.aspx go to Structure to generate your molecule then "Tools" then "Chemicalize" it wil give a bunch of parameters "Manage Calculations" then choose whatever you want pKa LogP LogD PSA Polarizability....blabla (play around ) I found it predict good chemical parameters but the "Predict Biological Activity" kind of suck.

here is LogD of one the aza-indoles you talk about

full data here:

http://www.chemicalize.org/structure/#!mol=CN%28C%29CCc1c[nH]c2cccnc12

good luck

 

[sekio]

with a logD in the negatives at physiological pH that is a death sentence for central activity...

4-Me-5-MeO DMT would be neat

 

[Friman1987]

DotChem: Thank you very much for this information.

New images:

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Physostigmine: https://en.wikipedia.org/wiki/Physostigmine
Ibogaine: https://en.wikipedia.org/wiki/Ibogaine
Some indole-alkaloids: https://uwm.edu/chemistry/people/cook-james/
PHA-57378
1. https://en.wikipedia.org/wiki/PHA-57378
2. https://patentscope.wipo.int/search...=&sortOption=&queryString=&tab=PCTDescription

Edit:

NSFW:

PNU-181731:
https://en.wikipedia.org/wiki/PNU-181731

Many of these molecules are enzyme inhibitors (ex MAO-I)

 

[DotChem]

with a logD in the negatives at physiological pH that is a death sentence for central activity...

that's what I thought.. a bit too polar but it could use active transport system of small molecules like pyridoxin to sneak in past BBB!

...
4-Me-5-MeO DMT would be neat

how about the methylenedioxyDMT??

like this:

or the aAMT analog

like this

 

[DotChem]

did I see Ibogaine mentioned by @Friman1987? my favorite psychedelic of all times..I thought about this sometime ago:

I wont touch the middle compound:

would probably be scopopalmine-like central M1 agonist nighmarish zombie visuals.. but it looks neat like BZP!

 

[DotChem]

read: scopolamine i.e. witchbrew https://en.wikipedia.org/wiki/Hyoscine_hydrobromide

 

[Friman1987]

Dotchem: Scopolamine is scary stuff.

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32 different ways to draw a phenethylamine (ex 2C-B):

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Those 32 differences should be the basic structure for drawing other phenethylamines. you can apply same thing on tryptamines. The effect should not be so predictable.

 

[Friman1987]

NSFW:

 

[aced126]

Dotchem: Scopolamine is scary stuff.

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32 different ways to draw a phenethylamine (ex 2C-B):

NSFW:

Those 32 differences should be the basic structure for drawing other phenethylamines. you can apply same thing on tryptamines. The effect should not be so predictable.

Not so sure about some of those prodrugs lol, you might wanna recheck those structures. Good phenethylamine structures tho, it seems not all of those have been synthesised and doing so would be a good step in understanding the phenethylamine SAR further.

 

[Friman1987]

Not so sure about some of those prodrugs lol, you might wanna recheck those structures. Good phenethylamine structures tho, it seems not all of those have been synthesised and doing so would be a good step in understanding the phenethylamine SAR further.

The last one is prodrug for DOB. Which one do you think will not work?
I know that N-MEO is not so good pro-drug for MDMA. But I do not know if the same think can apply for 2C-B, which is a bit more potent.
N-AC on mescaline dont work at all. But how about N-O-AC? I think N-O-AC should work.

 

[aced126]

What enzyme is meant to metabolise R-N-O-(C=O)-R?

 

[Friman1987]

(1) 2C-B-OH: N-OH on MDMA and several 2C-T (X) acts as a prodrug.

(2) N-MeO-2CB: I know that N-MEO is not so good pro-drug for MDMA. But I do not know if the same think can apply for 2C-B, which is a bit more potent. 2C-B have also not α-methyl and that maybe makes the demethylation more easier? That may not create steric hindrance for some enzymes.
I'm thinking about something like that:

(3) N-O-AC-2CB: I think something similar happens here too so you get 2CB-OH. I do not know what enzyme would do this so I understand what you saying haha. I have absolutely not any source on this one so there is no reliable facts behind those R-(N-O-AC)-R.


(4) Lis-2CB(Lysine+2CB): If the body recognizes it as peptides then it should metabolized by Proteases/peptidases otherwise by the hydrolytic activity of the red blood cells.

(5)

(6) α-C(O)OH-2CB: Should metabolized by decarboxylase as a normal amino acid, L-DOPA working in this way. Something that is interesting is that L-DOPA can cross the BBB while dopamine can not do this. It May happen something similar with α-C (O) OH 2CB. It should metabolize in both the CNS and PNS.

(7) α-C(O)OH-DOB: The last one is prodrug for DOB, Should metabolized the same way as Methyldopa, by decarboxylase.

 

[Incunabula]

Lisdexamphetamine inspired prodrugs seems to pop up with regularity in this thread. I doubt they'll ever make great psychedelics, but could they be used with a different intentl?

This is basically Shulgins "Eternity" or 2CE-5-EtO, which already has a very long duration, with a lysine attached to make the release longer and slower, so to be used as a nootropic. Lys-2CE-5EtO.

"The 5-EtO-homologue of 2C-E is 5-ethoxy-4-ethyl-2-methoxyphenethylamine, or 2CE-5ETO. The effective level of 2CE-5ETO is in the 10 to 15 milligram range. It is gentle, forgiving, and extremely long lived. Some 3 to 4 hours were needed to achieve plateau, and on occasion experiments were interrupted with Valium or Halcion at the 16 hour point. After a night's sleep, there were still some effects evident the next day. Thus, the dose is comparable to the parent compound 2C-E, but the duration is 2 to 3 times longer. It was given the nickname "Eternity" by one subject."

I'm not sure if alpha-methyl phenethylamines react similarly to 5-EtO substitution (more gentle, and a lot longer duration) but if they do, Lys-DOPr-5EtO might be even better suited as a nootropic.

 

[Solipsis]

That's pretty interesting... obviously made me curious about the release, onset delay, bioavailability... so seems relevant to quote this bit on the (animal) kinetics of vyvanse:

Oral administration of lisdexamfetamine dimesylate in comparison to d-amphetamine sulfate demonstrated that the bioavailability (AUC) of d-amphetamine from the prodrug was approximately equivalent near therapeutic human equivalent doses (HEDs). At high doses well above the therapeutic range, however, both AUC and Cmax of d-amphetamine from lisdexamfetamine dimesylate were substantially decreased in comparison to AUC and Cmax of d-amphetamine from d-amphetamine sulfate.

Absorption of lisdexamfetamine dimesylate orally administered increased non-linearly with increasing dose. The clearance of lisdexamfetamine dimesylate was greater than that of d-amphetamine following oral administration. When lisdexamfetamine dimesylate is administered via parenteral routes, there is delayed and gradual release of d-amphetamine with substantially attenuated peak concentrations when compared to immediate-release d-amphetamine.
Oral administration of lisdexamfetamine dimesylate demonstrated that lisdexamfetamine dimesylate was not detected in rat brain tissue. The major metabolites of lisdexamfetamine dimesylate following oral administration were glucuronidated amphetamine and amphetamine.
These two moieties comprised >90% of the total metabolites in plasma after oral dosing. Following intravenous administration, small amounts of hydroxylated lisdexamfetamine dimesylate were observed in plasma. As in the case of oral administration, the major metabolites from intravenous administration of lisdexamfetamine dimesylate were similar, glucuronidated amphetamine and amphetamine. In vitro experiments demonstrated that incubation of lisdexamfetamine dimesylate in human hepatic microsomal suspensions resulted in no significant inhibition of a panel of CYP450 isoforms that included CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, nor induction of CYP1A2, CYP2B6 or CYP3A4/5.
Lisdexamfetamine dimesylate is also unlikely to be involved in interactions with drugs
transported by the P-gp pump.
yada yada yada.

So this could produce a ceiling effect if someone were to 'lysinate' psychedelic amines? Could be very HR-y and helpful, but could also ruin it?

 

[DotChem]

New images:

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Edit:

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PNU-181731:
https://en.wikipedia.org/wiki/PNU-181731

Many of these molecules are enzyme inhibitors (ex MAO-I)

Why the images you post are not being displayed on my screen? "show" or "hide" just give blank page. Am I missing something?

 

[aced126]

Why the images you post are not being displayed on my screen? "show" or "hide" just give blank page. Am I missing something?

It works for me, you probably just need to update your browser.

 

[roi]

Hosted on imgur, do you somehow block the site?