Levophacetoperane

[clubcard]

The only country to make this a controlled drug is France. As you can see, it's simply the reversed ester of methylphenidate. The problem is that all 4 isomers have different activities - one is a sedative!. I guess you might be able to get the intermediate ketone in it's (R) form and an appropriate chiral reduction would give you the (R,R) alcohol that you then eterify. I don't know much about p-Me ethylphenidate, is it a serotonin releaser or an SND releaser?

I think it will be one of those interesting compounds that will never see the light of day.

The large paper on 'cocaine analogues' goes into methylphenidate/levophacetoperane analogues but sadly, the researcher didn't even check for serotonin activity. It's that kind of waste that is seen as totally acceptable to someone's PhD paper. In the old days, you would suggest a project to work with and your professor would say 'hey - since you are testing DAT & NET activity, you may as well check the SERT activity. After all, a PHD has to produce new, unknown facts to a high enough standard. We would have been chided for not checking the SERT. I guess it really has changed totally in 25 years.

Rather than a computer deciding likely scaffolds, a human, with all of their experience who would 'do a Janssen'. Just look at his Wiki page to see how many medicinal chemicals he got from 1 scaffold. Never let it be said '...a poor second to Belgium, when going abroad'.

 

[dopamimetic]

France also scheduled tianeptine - okay, it's an opioid (maybe a somewhat safe one), but one won't get much out of an entire bottle of it.

The problem is that all 4 isomers have different activities - one is a sedative!

Is the mechanism known by which that one isomer of MPH is sedating?

I don't know much about p-Me ethylphenidate, is it a serotonin releaser or an SND releaser?

Don't know about EPH, but 4-methyl methylphenidate apparently lacks any 5-HT activity (what I'd confirm from subjective impression, maybe very very light but probably none). Also it seems to be relatively weak as a DRI despite tight binding affinity (but this is just from wikipedia).

I'm curious about 4-fluoro MPH (why can't they do IPPD variants...!?) which became available recently. Don't expect much though.

 

[adder]

This is just a guess, but given the distance between the carbonyl oxygen and the amine's nitrogen, I suppose some kind of GABAergic activity might be responsible for sedative effects.

 

[clubcard]

WHY some isomers have sedative effects wasn't discussed in the patent (which is on the Wiki page), it was simply noted. I would indeed be perfect if the trans isomers could just be made producing an effect like Dexamyl (purple hearts).

It's a total pain to synthesize which is why no analogues have surfaced.