The 3D Fragment Consortium

Fragment-based screening comes up here fairly often (and if you're interested in the field, you should also have Practical Fragments on your reading list). One of the complaints both inside and outside the fragment world is that there are a lot of primary hits that fall into flat/aromatic chemical space (I know that those two don't overlap perfectly, but you know the sort of things I mean). The early fragment libraries were heavy in that sort of chemical matter, and the sort of collections you can buy still tend to be.

So people have talked about bringing in natural-product-like structures, and diversity-oriented-synthesis structures and other chemistries that make more three-dimensional systems. The commercial suppliers have been catching up with this trend, too, although some definitions of "three-dimensional" may not match yours. (Does a biphenyl derivative count, or is that what you're trying to get away from?)

The UK-based 3D Fragment Consortium has a paper out now in Drug Discovery Today that brings together a lot of references to work in this field. Even if you don't do fragment-based work, I think you'll find it interesting, because many of the same issues apply to larger molecules as well. How much return do you get for putting chiral centers into your molecules, on average? What about molecules with lots of saturated atoms that are still rather squashed and shapeless, versus ones full of aromatic carbons that carve out 3D space surprisingly well? Do different coll...

Source: In the Pipeline - August 8, 2013 Category: Chemists Tags: Drug Assays Source Type: blogs