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September 15, 2010
Talking about the amounts of compound to submit as a medicinal chemist brings up another topic. In every med-chem department I've worked in, there have been periodic exhortations for the chemists to register their intermediates. But too few people do.
For those outside the field, what I'm referring to are the "stepping stone" compounds along the way to structures that you're actually targeting. We try not to have these pathways go on too long, but there are often compounds that lack a key methyl group, or don't have the right stuff on the nitrogen yet, and so on. From the way that the compounds in a project have been running, you can be pretty sure that these things aren't going to be of much use for your current biological target - but the point is that they could be useful for someone else.
I've always been surprised by how many compounds sit on the benches, or in drawers, and never quite make it into the compound repository. To be sure, there are plenty of intermediates that shouldn't go in there - anyone who compound-codes a red-hot acid chloride should be whacked over the head. But plenty of things that people think of as "just starting material" or "just an intermediate" have nothing wrong with them, and should be added. I don't even mind a Boc group on an amine - t-butyl's not anyone's favorite, but there are plenty of drugs out there with carbamates on them. Fmoc is where I'd draw the line, though, since I think there's too much of a possibility for the binding to be driving by that big ol' fluorenyl, which is the first thing you'd want to get rid of if the compound hits. I don't think I'd go for any silyl groups on the alcohols, but benzyls and the like are fine.
So do a good deed today if you're in the lab: clear out a few of those compounds you have sitting around and put numbers on 'em. In your heart, you know it's the right thing to do!
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