Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
OK, since I’m a medicinal chemist, I have an excellent excuse to avoid the nitro functional group. It’s metabolic trouble, and although there are indeed drugs with nitros on them, they’re exceptions. Some of them, in fact, are antibacterials that rely on that metabolic activation to work, in the same way that there are nitrate… Read More
Here’s a safety warning for my fellow synthetic organic chemists. It’s a reagent combination whose hazards have been noted before, but a lot of people don’t seem to know about it: sodium hydride in DMSO or other polar aprotic solvents. And yeah, I’ve used that exact combination, too, many times. But I did those reactions… Read More
In today’s episode of “Fun With Chirality”, we have a look at phenomenon that could be very useful, come out of the blue, and which the very authors who report it have no explanation for. This is from a new paper in Angewandte Chemie from a team in Germany (TU-München) who have been looking at… Read More
Here’s another step along the way to automated synthesis, in a new paper from MIT. The eventual hope is to unite the software and the hardware in this area, both of which are developing these days, and come up with a system that can produce new compounds with a minimum of human intervention. Let’s stipulate… Read More
I’ve written several times here about phase-separated condensates in cells, but now comes a rarity: a paper with some evidence for a therapeutic application. Everyone in the field has been thinking along such lines, naturally, but this is the first small-molecule screen that I’ve seen that tries to tie modifying condensate behavior in t… Read More
Here’s a ring system that you’ve never used before – the cyclopropyl system in purple at the end of the row in the diagram at right. It’s described in this paper from GSK-Stevenage as a new morpholine isostere. A 4-morpholino-pyrimidine hinge binder core is preferred in many PI3K and PIKK inhibitors, but the team was… Read More
This is a pretty interesting paper on several levels. It sheds light on Mucin I kidney disease (MKD), on protein degradation pathways (a hot topic these days, as those in the industry well know), and it also provides a small molecule lead compound. It’s a large multicenter team, starting off with the Broad Institute, but… Read More
Organic chemists are used to breaking and forming all sorts of chemical bonds; it’s what we do. But to do that we have to mess around with the energetics, because many (most!) of these processes don’t happen fast enough or selectively enough on their own. (In fact, the fundamental idea of “click” reactions, as introduced… Read More
A former colleague was telling me the other day about some not-so-pleasant surprises that occurred when he was helping to clean out a lab that hadn’t had some cabinets opened in a while, and I think many readers will have had such experiences. Academic labs are particularly prone to Easter eggs of this sort, since… Read More
Let’s talk crystals for a few minutes. Those of us (like me) who are familiar with chemistry and biology, but who are not crystallographers themselves, will know the broad outlines of X-ray crystallography, and can appreciate its extension to diffracting electrons instead of X-rays. But there are a lot of odd and subtle things that… Read More
