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February 19, 2010
Two For One Sale
A double complaint this morning, and both from the same literature item - if I were charging anything for the blog, I'd say that it's delivering value for the money. At any rate, the first kvetch is something that I know that many chemists have noticed when reading more biology/medical-oriented journals. You'll see some paper that talks about a new compound that does X, Y, and Z. It'll be named with some sort of code, and they'll tell you all about its interesting effects. . .but they don't get around to actually telling you what the damned stuff is.
As I say, this is a chemist's complaint. Many biologists are fine stipulating that there's a compound that will do these interesting things, because they're mostly interested in hearing about the interesting things themselves. It could just be Compound X as far as they're concerned. But chemists want to see what kind of structure it is that causes all these publication-worthy results, and sometimes we go away disappointed.
Or we have to dig. Take this PNAS paper on a broad-spectrum antiviral compound, LJ001. It looks quite interesting, with effects on a number of different viral types, and through a unique mechanism that targets viral membranes. But what is it? You'll look in vain through the whole paper to find out - that compound is LJ001 to you, Jack. You have to go to the supplemental material to find out, and to page 10 at that.
And that brings up the second complaint. LJ001 turns out to be a rhodanine, and regular readers will note that earlier this month some time was spent here talking about just how ugly and undesirable those are. It's very, very hard to get anyone in the drug business to take a compound in that class seriously, because they have such a poor track record. Looking over the small SAR table provided, I note that if you switch that thioamide group (the part that the chemists hate the most) to a regular amide, turning the thing into an thiazolidinedione, you lose all the activity.
TZDs aren't everyone's favorite group, but at least they've made it into marketed drugs. Rhodanines are no one's favorite group, and it would be a good thing of the authors of these papers would realize that, or at least acknowledge it if they do. It's not an irrational prejudice.
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