So I enjoyed this paper very much, but it starts off with a claim that’s worth arguing about: “organic synthesis is still a rate-limiting factor in drug-discovery projects“. Is that true?

It depends on where you’re standing. All the synthetic limitations described above are real, and they keep us from being able to make a lot of molecules that we’d otherwise be cranking out. But (and this is a big point) it’s rarely the case that we medicinal chemists identify a tricky new structure that absolutely has to be made. That sounds odd, but it comes down to our predictive powers, which aren’t so great. We don’t generally draw some wild compound up on the hood sash and say “That’s the one, folks: find a way to make it or die trying”. We never know which is the one, so in the absence of knowing, we make the things that we can make in the ways that we can make them, and honestly, much of the time, we can manage to come up with something.

• Uncategorized