CRL-40,941 - fluorinated adrafinil

[Phener]

http://en.wikipedia.org/wiki/CRL-40941

http://www.google.com/patents?vid=4489095

Very little information in the patent, can't seem to find any information on pubmed or google.

Patent and Wiki suggests 2x potency of adrafinil but with additional "anti-agressive" effects.

The anti-agressive effects - anyone have any predictions?

From recently reading that modafinil might have D2 partial agonist properties:
http://www3.interscience.wiley.com/journal/122359005/abstract?CRETRY=1&SRETRY=0

I'm thinking maybe adding a Fluorine increases the tendency to become more like an antagonist?? but with the combined DRI properties might still be nootropic. Maybe a new antipsychotic nootropic! 8)

 

[hamhurricane]

that is interesting, i wonder if more halogen subs have been tested? modafinil is a pretty perfect (but boring (ie non euphoric)) stimulant - marginally better than caffeine - which is better than the majority of RC stimulants out there. modafinil's major downside is its low potency, i wonder about the bis(p-methyl) analog as well...

 

[MurphyClox]

Interesting finding!
When I see fluorine in a synthetic bioactive molecule, I have instantly to think that it is intended to slow down resp. hamper metabolism. Well, not in this case, as modafinils metabolism goes practically only via modification on the amide-part (resp. hydroxamic acid-part in adrafinil).

Fluorine is of course used for other reasons, too. Maybe increase in lipophilicity was desired while remaining the concomitant increase in steric bulk to a minimum (fluorine is quite small). I dunno...


- Murphy

 

[Phener]

^what surprised me with this one was they were using adrafanil analogues not modafinil, would have thought going straight to modafinil would be the logical approach.


You would presume with the success of modafinil that playing around with substutions on the two phenyl rings would be the first port of call. I dont have time to trawl through all patents but assume cephalon are doing this, well if they have any sense (although classic pharmaceutical company approach of lets market the pure racemic molecule Armodafinil for all the non-FDA approved and current unapproved uses of modafinil) - money, money, money


could always add TWO thiophene groups! Result: Not only urine smelling of asparagus but whole body smelling of asparagus!

 

[seep]

^what surprised me with this one was they were using adrafanil analogues not modafinil, would have thought going straight to modafinil would be the logical approach.

I think adrafinil was developed before modafinil. The prodrug is hepatotoxic, so I'm not sure if the parafluoro substitutions attenuate or exacerbate this effect. I assume Cephalon explored these and other variations for modafinil and armodafinil, but I'm too lazy to go spelunking.

Maybe a new antipsychotic nootropic!

See the PDE4 inhibitor rolipram

 

[vecktor]

I think adrafinil was developed before modafinil. The prodrug is hepatotoxic, so I'm not sure if the parafluoro substitutions attenuate or exacerbate this effect. I assume Cephalon explored these and other variations for modafinil and armodafinil, but I'm too lazy to go spelunking.

See the PDE4 inhibitor rolipram

from what I can determine lab lafon did a lot of work and most of the interesting work on these whereas cephalon have spent most of their time coming up with ingenious and devious to extend their patent, to market it for off label uses and suing generic manufactuers.

there is reference to 4,4-dichloromodafinil somewhere.