Structure modification of 2-dpmp (aka desoxypipradrol)

[Smyth2]

I was wondering if 2-dpmp (aka desoxypipradrol) could by modified by going from a piperidine basic skeleton to a morpholine. I saw some SAR one time (I think by HM Deutsch) which showed that for Ritalin this modification is not tolerated, but 2-dpmp is a different compound altogether.

Just wondering what the effects of this subtle modification are likely to be. I know that the half-life would be altered significantly but I was wondering if the compound would still be active at low dose.

 

[fastandbulbous]

The morholine derivative is actually more potent. There's a paper somewhere about modifications of the heterocyclic ring, but can I hell remember it's title

 

[immad]

Would it reduce the half life though? That's the main problem of desoxypipradrol.

 

[negrogesic]

More potent.........curious.......

 

[Smyth2]

I just thought of a second compound that looks fairly tasty/promising. I'm not too sure how it could be made but we are only looking at the target molecule and needent concern ourselves with the synthesis discussion.

 

[fastandbulbous]

Replacing one of the phenyl groups with a three atom long chain retains activity with only a moderate reduction in potency. What it does do though is alter the half life. The ethoxy compound above had chance to still have a fairly long half life, but nowhere near that of desoxy. The shortest half lives belong to methylphenidate and it's reverse ester (levacetoperane), which both have a 3 atom long chain, but one that can be easily metabolized. A propyl chain had chance to give a compound with a half life not much shorter than desoxy as it'll be a bastard to find a point of metabolic attack

 

[nuke]

Making the 6 member ring with the amine into a 5 member ring (piperidine -> pyrrolidine) also decreases duration by about 30-50%