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July 6, 2004
Lighting Out for the Frontier
Next week I'll be on vacation, and this week I find myself flogging the chemistry databases. We're looking at a new series of compounds with some interesting activity, and they're easy to make. That's the problem.
They're so easy to make that everyone has made them. That means trouble, because there's so much prior art (and so many potentially interfering claims) that we'd have a difficult time getting a patent position. There are quite a few popular structural classes with this problem: piperazines, indoles, and imidazoles have been trampled flat, for example, and try getting (for example) a claim in some of the benzofuran compound space that Lilly has staked out. Not fun.
So we're looking to change the inner parts of the structure in some non-obvious way and thus stake out a position with some elbow room in it. It's not easy - for one thing, things are to the point that some of the obvious paths to elbow room have already been worn out a little. And you don't want to come up with new ones that are going to take fourteen steps to make, either. That's because it's unclear whether the interesting activity that got us here will persist once we start chopping and rearranging.
Often it doesn't. You feel like a real idiot - even if you aren't - when you spend a lot of time on a series like that and none of the compounds are active. And you feel as if you've wasted our time, because you have. "Fail quickly" is one of the basic mottos of medicinal chemistry.
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