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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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« Avastin's Numbers | Main | Random Questions, Answered Randomly »

June 9, 2009

Instant Med-Chem Wisdom

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Posted by Derek

I didn't note it here when it came out last year, but I wanted to recommend this paper to all the readers who are medicinal chemists. It's an effort by M. Paul Gleeson of GSK to generalize some rules from huge piles of oral dosing data in the company's files. It's all boiled down to a set of charts, for different classes of compounds (neutral, acidic, basic, and zwitterionic), and you can see the effects of changing molecular weight and/or polarity on things like bioavailibility, potential for hERG problems, clearance, etc.

There are no major surprises in the charts. But it's very useful to have all these "rules of thumb" in one spot, and to have them backed up by plenty of data. For experienced medicinal chemists, it's a distillation of everything that we should have been learning. And for those starting out, it's a way to get a fast understanding of what matters when you're making new structures. Check it out!

Update: for a much more sceptical take, see here.

Comments (4) + TrackBacks (0) | Category: Life in the Drug Labs | Pharmacokinetics


1. Great Molecular Crapshoot on June 9, 2009 2:39 PM writes...

I reviewed this about a year ago and must admit to being somewhat underwhelmed by the analysis. Here's the link if folk are interested:

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2. Teuta9 on June 9, 2009 2:46 PM writes...

For me, a very useful paper... but a real shame that it's also another example of the flood of "rediscovery of MedChem common sense" publications that have appeared in the last 2 years or so. Why? Because the same R&D managers who learnt nothing/forgot nothing in the HTS/CombiChem cul-de-sac have been recently filletting out almost 2 generations worth of "real" MedChem experience from those same's Year Zero for Big Pharma (all over again!)

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3. Paul S on June 9, 2009 2:52 PM writes...

That is a superlative resource. Many thanks.

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4. Morten G on June 11, 2009 3:01 AM writes...

Which one? The Gleeson paper or the Great Molecular Crapshoot?

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