N-Ethyl benzodiazepines?

[so nostalgic]

Does anybody know how N-Ethyl benzos would differ from their N-Methyl or desmethyl counterparts?

More specifically something like NEthyl Nitrazepam vs N-Methyl Nitrazepam or Nitrazepam?

 

[izo]

Never seen one, I think there is one even sold with a trifluoro or fluoroethyl group, don’t remember the name, have to look it up on wiki.

 

[izo]

I meant halazepam.

 

[Fertile]

Well, halazepam has a 1,1,1-trifluoroethyl amide moiety which is not quite the same.

In short, even by the 1960s, N-methyl was identified to produce the highest activity in 3 ring benzodiazepines. There are a number of benzodiazepines with different N-methyl groups but in all cases this is to adjust the ADME and that the nor compounds are the active.

I mean, you can go for even larger substitutions that actually INCREASE affinity but reduce agonism i.e. high-affinity, low-efficacy.

The Stenbach group really did interrogate the QSAR of 3-ring benzodiazepines, the Cook group did the same with 4-ring derivatives and their are papers on the QSAR of the bioisosters that use a different aromatic. The information IS out there and AFAIK IS free.