Here's an interesting paper that some of you may have seen in J. Med. Chem.: "Heteroaromatic Rings of the Future". That's an odd title, but an appropriate one.
For the non-chemists in the crowd who made it to this paragraph, heteroaromatic rings are a very wide class of organic compounds. They're flat cyclic structures with one or more nitrogen, oxygen, or sulfur atoms in the ring - I'll leave out explaining the concept of "aromaticity" for now, but suffice it to say that it makes them flat and gives them some other distinct properties. These structures are especially important in medicinal chemistry. If you stripped out all the drugs that contain something from this class, you'd lose a bit under half of the current pharmacopoeia, and that share has lately been increasing.
The authors have sat down and attempted to work out computationally all the possible heteroaromatic systems. If you include a carbonyl group as a component of the ring, you get 23,895 different scaffolds (and only 2986 if you leave the carbonyl out of it). Their methods to define and predict that adjective "possible" are extensive and worth reading if you're curious; they did put a lot of effort into that question, and their assumptions seem realistic to me. (For example, right off, they only considered mono- and bicyclic systems, 5- and 6-membered only, C, H, N, O and S).
At any rate, only 1701 of those 23,985 have ever been reported in the literature. And it looks as if reports of new ring systems reached a peak in the late 1970s, and have either dropped off or (at the very least) never exceeded those heights since then. The authors estimate that perhaps 3,000 of their list are synthetically feasible, with a few hundred of them being notably more likely than the rest. Their paper, in fact, seems to be a brief to alter that publication trend by explicitly pointing out unexplored synthetic territory. It wouldn't surprise me if they go back in a few years to see if they were able to cause an inflection point.
I hope they do. I'm a great believer in the idea that we medicinal chemists need all the help we can get, and if there are reasonable ring systems out there that we're not exploiting, then we should get to them. Adventurous chemists should have a look.