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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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In the Pipeline

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October 7, 2002

Idle Hands

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Posted by Derek

Events don't leave me much time to blog tonight, and I'm staying busy at work as well. Without going into job-terminating levels of detail, I'll say that we're at the stage now where we not only have to worry about what molecules to make, but how we're going to make them.

Those of you in the field know what I'm talking about. There are any number of ways to make complex molecules if you're just looking to finish with a few milligrams. Big natural products syntheses never finish with more than that, because the earlier stages would have to be performed in a cement mixer. But for the smaller, more drug-like molecules that labs like mine are supposed to turn out, we can only get away with making small amounts for so long. It's fine for the earlier stages of a project, but eventually you'll need more.

If your stuff starts to look interesting, then everyone wants a vial of it. More assays, more animal tests, more safety and formulation and toxicity tests - folks just come out of the floor grates reaching for the stuff. (Medicinal chemists always complain that some of the other departments go through our compounds as if they thought we had barrels with metal scoops chained to them.) That means that a synthesis has to be worked out that can provide gram quantities of material (without having to make people work night and day like they were in graduate school.)

So it has to work well, and work every time, and work in a way that any reasonably competent chemist can sit right down and do it, too. As the compound needs increase, the constraints on the chemistry get more esoteric: can't use that solvent, because we can't get tank cars of it. Can't use that reagent, because the waste stream it generates is too expensive. Can't use that reaction, because once every hundred times it could take off and ventilate the place. We're not at the stage where we have to worry about such things - yet. I hope we end up having to, though, because those sorts of worries are the ones that attach to compounds that can become drugs.

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