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I Like to Draw Pictures of Random Molecules

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z748MhZ.png
 
Nexus_Tripper said:
2C-Ts are not chiral and are still MAOIs.
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yeah i realized i left it ambiguous, didn't change it due to laziness... figured it would be apparent that i was referring to chirality of the alpha-methyl-phenethylamines.

the fact that 2C-Ts are not chiral and are MAOIs does not allow us to predict whether or not the R- and S- enatiomers of the 3carbon ones are both MAOIs. imagine it like a skeleton key that fits every lock, and its not til you start adding extra pegs to the shaft that it starts being specific to certain locks...
 
pharmakos said:
i'm definitely interested in caffeine analogues, Mr. K. Love. caffeine is arguably the greatest drug their is when looked at in terms of cost vs. benefit. improving on it would be wonderful.
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Good lord, there are a lot of them. Here using the term "caffeine analogue" a little loosely, but there is a whole pretty wild and interesting world around xanthine adenosine antagonists that I wasn't at all aware of ...

First up and very cool, some SAR stuff:

16a1e7l.png


From here. Lots of other good stuff.

Here's a good and more recent (looks like there was a lot of work done on this in the 80s) review:

Müller C, Jacobson KA. Xanthines as Adenosine Receptor Antagonists. Handb Exp Pharmacol. 2011; (200): 10.1007/978-3-642-13443-2_6. doi: 10.1007/978-3-642-13443-2_6

This paper is a tour de force if you're interested in exotic xanthine derivatives (tricyclic xanthines! see spoiler below), has a shocking number of analogues, affinities for all of them, and has sort of a "everything you wanted to know but were afraid to ask" vibe, even discussion about some applications. I was thinking about trying to draw my own caffeine analogue but all of them are probably there already.

Tricyclic xanthines a/k/a so that's where the MDIO goes ;) ...

nihms539795f6.jpg

Daly JW. Caffeine analogs: biomedical impact. Cell Mol Life Sci. 2007 Aug;64(16):2153-69.

Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.
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Bruns RF, Daly JW, Synder SH. Adenosine receptor binding: structure-activity analysis generates extremely potent xanthine antagonists. Proc Natl Acad Sci U S A. 1983 Apr; 80(7): 2077–2080.

Highlight: Meet 1,3-dipropyl-8-(2-amino-4-chlorophenyl) xanthine, "a compound of extraordinary receptor affinity, with a Ki for adenosine A1 receptors of 22 pM. It is 4,000,000 times more potent than xanthine itself and 70,000 times more potent than theophylline."

1%2C3-dipropyl-8-(2-amino-4-chlorophenyl)%20xanthine.png


So basically, the ohmefentanyl of adenosine antagonists. Impressive. It's quite a receptor probe but as a drug who knows. I'm going to study this one further.

Maybe back with more later.
 
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Can see these compounds being used widely in medicine and don't really know why there isn't more research going into this.
 
This is an interesting one. Potent, very high selectivity for A1. This could be useful in the NICU and maybe in treating hypoperfusion, shock? Water soluble.

8-(2-amino-4-chlorophenyl)-1,3-dipropylxanthine (ACPDPX)

%208-(2-amino-4-chlorophenyl)-1%2C3-dipropylxanthine.png


This is another potent highly A1-selective xanthine but it is probably less useful to medicine by way of not being water soluble so not suitable for IV drip, etc.

1,3-Dipropyl-8-cyclopentylxanthine (DCPCX)

1%2C3-Dipropyl-8-cyclopentylxanthine.png


But now it gets weird, and Bluelightish ... it has been researched as potentiating MDMA and DOI (inb4 it winds up in pressed pills...is the caffeine in pressed pills already doing this?)
 
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And, on the other side, this rather baroque molecule ..

1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl)]xanthine

1%2C3%2C7-Trimethyl-8-%5B(3-carboxy-1-oxopropyl)amino%5D%20styrylxanthine.png


Potent, A2 selective. Water soluble.

Good for asthma/bronchospasm?
 
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Beats me.

* **

I bomb atomically. Socrates' philosophy and hypotheses couldn't stop these lyrical armed robberies...

1-(1-piperidinyl)-1-(indol-3-yl)cyclohexane.png
 
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When researching some unrelated things I came across this oddity:

Diphenyl(piperidin-4-yl)methanol.png


Azacyclonol is a positional isomer of pipradrol. Rather than being yet another NDRI or something that would inspire f&b to invade Poland, it is a mild sedative that has the peculiar quality of attenuating psychedelic experiences, although it's not a tranquilizer or an anti-psychotic. Was tried with schizophrenics in Europe with limited success and sailed into the sunset.

Perhaps something that could go in the druggie's emergency bag (I used to have one when I was actively experimenting with stuff: it started like this - Narcan, flumazenil, Thorazine, Ativan, Haldol ...)
 
aced126 said:
SKL said:
Dresden said:
2-methylamino-1-(4-pentylphenyl)propane.png
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Amfepentorex. Yet another market withdrawn anorectic.
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Does this one release or reuptake DA?
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Boy, that sent me a bit down the rabbit-hole, and I'm a bit intrigued. I knew the soundbite, and it's available on Wiki, but trying to dig deeper, I can find next to nothing about amfepentorex and it's pharmacology via the usual venues, but haven't found much.

There's not a lot of useful information I could readily find about it, except for the basics, it was marketed in France as an appetite suppressant, etc., save a few references that I think I'd have to track down in print (fortunately I have access to a wonderful public library here in the City that stocks 1960s era Chimica Therapeutica, Vol. 2, Pg. 260, 196, if that will help at all ....)

Now, this is a pretty interesting chemical, actually. Question being, how far can we take single ring substituted amphetamines? A lot of us will be familiar with 4-methyl-AMP, which by all accounts wasn't very impressive, and is more serotonergic than anything else, I've actually seen some contradictory reports as to whether it's a serotonin/dopamine releaser or an S(N?)DRI. The EMCDDA has a pretty solid report about it. This of course, is without the N-methyl. 4-methyl-MA is a metabolite of mephedrone, and has some role in it's activity I figure, but sounds kind of toxic. So I guess the question is, what do we get by the N-methyl and particularly elongating the chain at the 4 position? If I can only hazard a guess I think this molecule might have some significant serotonergic activity which might well have to do with it's utility as an appetite suppressant, a la locaserin (which see, is an also interesting molecule ...), but evidently retains some dopaminergic/amphetamine type actions as well. I've really had some trouble locating specific information about this molecule, it seems rather forgotten, although the time I've spent is limited. My interest is a bit piqued though. More later maybe. I'd love to know any sort of subjective account of this experience or of course more details about it's pharmacology/SAR (which as far as my limited knowledge goes suggests it may be a bit serotonergic, maybe more towards being a reuptake inhibitor?)

(1R)-8-chloro-1-methyl-2%2C3%2C4%2C5-tetrahydro-1H-3-benzazepine.png

not related but interesting in it's own right
this is primarily serotonergic
and a controlled substance in the USA
allegedly has some psychedelic-ish effects in high doses
but who would really want to?
 
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