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.