• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Changing Desoxypipradrols T1/2

Status
Not open for further replies.
Reminisant B

Reminisant B

Greenlighter
Joined
Nov 3, 2005
Messages
401
One of the main potential problems with desoxypipradrol (can be argued) is it's long half life.

As clearly adding the hydroxy group makes a controlled drug (pipradrol), what about adding a methylenedioxy group on one of the phenyl rings?

Not in order to make an entactogen but to give the bodies metabolic processes something to grapple on with in order to produce more polar metabolites and therefore shorter half-life?

(Appologies if this has been discussed before, couldn't find discussion)
 

Attachments

  • MDDP.png
    MDDP.png
    2.4 KB · Views: 132
Well adding a -OH group somewhere else than on the pipradrol skeleton seems to work, but of course, if you can make it more MDMA like AND reduce T1/2 then thats better.

sch.jpg


Actually, where does this stuff bind?
 
Last edited:
The problem with Sch-5472 is the variable, unreliable activity. A dose just right for person A is too strong for person B, while person C experiences hardly any effect.

Adding a methylenedioxy group to desoxypipradrol would most likely render it inactive.

All these types of stimulants bind to and block the dopamine transporter in some way. Of course there are stimulants (caffeine, modafinil, amphetamine) with a different mechanism of action.

An interesting compound in this series is 3-(bis(3-fluorophenyl)methyl)piperidine, because it's a fairly potent dopamine reuptake inhibitor (Ki = 30nM) and a NMDA antagonist (Ki = 167nM). That could give a nice synergy.
 
+dopamine -NMDA? Isn't that like tiletamine? Esterification of Sch-5472 might be interesting... making it pass the BBB more effectivly...
 
Ah yes had forgotten about sch-5472


Isn't 3,4-dichloromethylphenidate meant to be a more potent version of methylphenidate?

If so would that not suggest a methylenedioxy group on desoxypipradrol or methylphenidate would still show activity?
 
do you substitute 1 ring or both? Does the binding work on an asymetrical site so that it will sort itself out. I would be interested to know about the MD analog, but not so interested that I would bother making it. The MD goes for seratonin and these diaryl things go for dopamine, do they not?
 
Was referring to just one ring but I guess desoxypipradrol is considerably different from methylphenidate so analogies can't be made.

I guess fairly uncharted territory with ring substituted desoxypipradrol analogues
 
Even if it means more background research (instead of suggesting every conceivable chemical modification which seems to be the theme of this board), it would be much more effective if (ie - probably wont achieve stated goal unless) you have some information about what enzymes are used for metabolic inactivation and aim towards making it a better substrate for 'em. Same conceptual approach as DOTFM (except, you know... shortening the action)
 
Last edited:
How about adding methyl groups to either one of the phenyl rings. (depending on the synthesis method, it may be easier/more difficult)
Hopefully these could be metabolised to carboxyl groups a'la methylbenzene/toluene, leading to speedier elimination by increasing the solubility in water and blocking re-entry to the CNS (as that big bulky polar COOH isn't going to get past the BBB again)
 
The only reason why desoxypipradol made it to the market is that it's a simple one-step synthesis (hydrogenation) from a cheap, commercially availabe intermediate. Anything that is designed to have a shorter T 1/2 would require a much more complicated and costly synthesis that's beyond the guys who are now selling desoxy.
 
What, from diphenyl-2-pyridylmethane ? Yeah, I suppose that hydrogenation is quite easy.
 
Only thing I cabn think of is to acidify the plasma to prevent reabsorbtion of the unionozed form from the bladder ie a big glass of orange, grapefruit or for those brave (& someone masochistic souls) lemon juice. Like a minor league version of forced acid diuresis
 
Wouldn't you just down some glacial acetic acid in gelcaps, or something?
Or citric acid in gelpcaps?
Why torture yourself with lemon juice...
 
this is insane.

this drug has a long half life. this drug is stupid cheap and available but its half life is too long to be desirable which leaves 3 options,

1 forget about D
2 alter the structure of drug D to shorten the half life. hint the hydrogen between the two phenyls is acidic, also look at how 2-benzhydryl pyridine is made......

3 Fuck with the pH of your body to increase the clearance of D.

2 is the best option
followed by 1 and 3.
 
Status
Not open for further replies.
Top