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Author Topic: Designer Takeoffs on Caffeine  (Read 273 times)

RVM45

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Designer Takeoffs on Caffeine
« on: July 27, 2009, 12:56:14 AM »
Does anyone know if there's ever been any work in designing "Designer Drugs" by making minor substitutions on the Caffeine Molecule?

I mean, what happens if you subtract a Hydrogen Atom There and substitute an NH2; or an Fe; Or a hydroxyle group...?

You know, those kinda substitutions...

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Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #1 on: July 27, 2009, 01:14:40 AM »
Seeing that an oxidation of the Pi bond across the two nitrogens of caffeine would lead to basicly a tri-methylated version of uric acid I would proceed with great caution before testing any caffeine analog due to chances of problems simular to gout and the likes. Best to understand the pharmacology of caffeine fully before even undertaking such an experiment. I have studied this somewhat more indepth years ago and do not really feel its a worth while venture. Caffine works by blocking action at the adenosine receptors leading to things such as vasodilatation and blocking adenosines ability to cause fatigue.

I have some more information on this subject but I am a bit busy at the moment so if you stop back later I could perhaps shed some more light on this subject even though its been some years since I studied it fully.

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Vesp

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Re: Designer Takeoffs on Caffeine
« Reply #2 on: July 27, 2009, 10:52:23 PM »
Don't forget about theophylline, and theobromine when it comes to analogues of caffeine.
Looking around a bit I also found one called paraxanthine. It looks pretty interesting to me. http://en.wikipedia.org/wiki/Paraxanthine

This, http://en.wikipedia.org/wiki/Xanthine, is the base compound of them all and is possibly a good starting point for analogues.

I remember there being a decent thread on the synthesis of caffeine, but mostly theobromine on SM, you may be able to find that and substitute the appropriate reagents to get some nifty analogues.

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Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #3 on: July 27, 2009, 11:20:31 PM »
The grand pappy of all these compounds is purine and this can be synthesised by heating Formamide for an extended period at higher temperatures in like 70% yeilds IIRC. Once you have purine its a matter of adding things where you want them. I wouldn't mind seeing a sulfur analog to Caffeine.
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Douchermann

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Re: Designer Takeoffs on Caffeine
« Reply #4 on: July 28, 2009, 07:41:57 PM »
I think it would be interesting if someone were to venture deply into it, and try add more advanced things than simple methyl groups or metal ions.  Perhaps, N methyl chains, or N,N dimethyl chains.  Even attempts at analogue phenethylamines would be interesting.  I don't see it likely to create anything interesting, but hell, worth a shot, eh?

Enkidu

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Re: Designer Takeoffs on Caffeine
« Reply #5 on: July 29, 2009, 06:30:08 PM »
Actually, the purine could, theoretically be adapted to be a 5-ht2a partial agonist. There are some papers I posted at SM.

Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #6 on: July 29, 2009, 06:58:04 PM »
I ran a search over at Science madness for purine but returned only one irrelavent hit. Would you be able repost the reference for this.

I find it strange that it would posses that kind of activity since its pretty removed from most other substances I have seen with the same affinity.
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Enkidu

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Re: Designer Takeoffs on Caffeine
« Reply #7 on: July 29, 2009, 08:16:39 PM »
Might have been at the dark side, or maybe I didn't post them at all. Have to go now, I'll look later.

Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #8 on: July 29, 2009, 08:42:20 PM »
This is all I could turn up over at BL interesting though. It cool to give me a rough idea on what structure is being used to fill the receptor. Its good to see there can be 5HT activity of purine analogs because that gives it more potential then I once thought.

@RMV45

If you don't mind figuring out strutural properties for your self here is 14  Pubchem results for bioactive compounds that where tested that have Caffeine as the substructure.

Reference: Pubchem search results
« Last Edit: July 29, 2009, 10:07:37 PM by Sedit »
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2bfrank

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Re: Designer Takeoffs on Caffeine
« Reply #9 on: July 29, 2009, 11:51:24 PM »
Quote from: Sedit on July 27, 2009, 11:20:31 PM
The grand pappy of all these compounds is purine and this can be synthesised by heating Formamide for an extended period at higher temperatures in like 70% yeilds IIRC. Once you have purine its a matter of adding things where you want them. I wouldn't mind seeing a sulfur analog to Caffeine.

Sedit, do you think a methyl group could be added - removed from something else. I reckon thats been pondered.

Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #10 on: July 30, 2009, 12:14:54 AM »
Yes of course and that is the results of many other natural stimulants such as theobromine. It is metabolised to the following invitro



You can clearly see how it effects adenosine in this photo also from wiki.


This gives a starting point in understanding how substituted purines can cause greater amounts of energy by blocking the endogenus agonist and force a greater level of alertness. Perhaps Caffeine with the same moiarity as Adenosine on the ring would produce a stronger affinity and longer action of caffeine.  The starting material of choice here would prove to be Theophyllin.

Please note though that I feel if any recreational activity will be found here it would be substitutions of what ever compound Enkidu speaks of that has 5HT2A affinity
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2bfrank

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Re: Designer Takeoffs on Caffeine
« Reply #11 on: July 30, 2009, 02:22:14 AM »
Cool, I was thinking though of the formamide > unsubstituted purine, for itself - somehow - to promote o-demythylation of perhaps a wide variety of compounds. Just a thought.

Also - Thanks though for presenting what you have, It is good to see these transformations, visually, plus of course the bio-activity type relationships. I am currently doing a biochem metabolism unit, hence learning some of the pathways associated with these types of molecules.  So much memory work though.
« Last Edit: July 30, 2009, 04:02:36 AM by 2bfrank »

Sedit

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Re: Designer Takeoffs on Caffeine
« Reply #12 on: September 02, 2009, 08:10:20 PM »
Over at PN someone recently brought up the topic of a caffeine derivitive that was unknown to me. Its name is theacrine and interestingly enough it is a seditive/hypnotic. It is the tetramethylated variant of caffeine and its synthesis would seem pretty straight forward for anyone skilled in the art of methylation reagents.

Wounder what effects would be gained from the Ethylated variant. I have some EtBr sitting around going to waste.


He has also mentioned but provided no source for the synthesis of NH3 and Methylamine from the reaction of caffeine + NaOH. Has anyone else ever come across this?
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Vesp

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Re: Designer Takeoffs on Caffeine
« Reply #13 on: September 02, 2009, 09:42:44 PM »
I've never heard of that methylamine synth before, though caffeine is easy to get in pure at certain places and would be interesting to try.

That is really interesting about the sedative/hypnotic. It must do the something close to the opposite of what caffeine does then, instead of blocking the adenosine receptors, it might activate them or some how make the adenosine present more active by altering the structure of the receptor?
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