Also from this week's C&EN, a terribly interesting article by Carmen Drahl on the process of giving a generic name for a compound:
A list of naming rules, some of them quirky, has evolved as well. The letters h, j, k, and w are off-limits because they lead to pronunciation problems in other languages. Drugmakers can suggest names to the USAN Council, but any name with an implication that a drug is better, newer, or more effective than the competition heads straight for the reject pile, Shubat says. When a prospective name reaches the WHO stage, international connotations come into play. A name that sounds perfectly fine in English might have bad or even obscene connotations elsewhere. No one wants to sell the Chevy Nova of the drug world.
The crux of the generic-naming system is a collection of short name fragments called stems. Each stem has a meaning connected to a particular drug class or mode of action. The official list of USAN and INN stems and substems has grown and changed over time as companies come up with new classes of drugs, Shubat explains.
Understanding drug names through stems is a lot like learning English vocabulary by studying Greek and Latin roots. Learn what the stems mean, and you’re most of the way to figuring out what a drug does. Take top-selling drug Nexium, which has a generic name of esomeprazole. The stem in that name is -prazole, which means the drug is a benzimidazole antiulcer agent. The drug’s es- prefix describes the nature of the drug’s chirality—esomeprazole is dextrorotatory and contains a chiral center in the S configuration.There's also a blogpost from Carmen at The Haystack about how dasatinib got its name from BMS research fellow Jagabandhu Das, even though he didn't invent the molecule:
So how’d Das make a difference? About one and a half years into the search for a kinase inhibitor that might be able to treat chronic myelogenous leukemia, “we were hitting a wall,” Barrish, today vice-president of medicinal chemistry at BMS, recalls. “We couldn’t get past a certain level of potency.”
Early on, the team’s work suggested that a 4′-methyl thiazole was critical for potency. Replace the methyl with a hydrogen, and potency went out the window. But Das challenged that dogma, Barrish says. He thought the compound series had evolved to the point where it would be a good idea to go back and test those early assumptions. His hunch paid off – in the new, later kinase inhibitor series, it turned out that removing the methyl group from the thiazole actually boosted potency. Thanks in large part to that discovery, the team eventually was able to make kinase inhibitors with ten thousand fold higher activity.
“Jag didn’t stop there,” Barrish says. After debunking the methyl dogma, Das found a way to replace an undesirable urea moiety in the team’s inhibitors with a pyrimidine group, which improved the inhibitors’ physical properties. With help from Das’s two insights combined, eventually BMS’s team came up with the molecule that became dasatinib (J. Med. Chem., DOI: 10.1021/jm060727j).There's nothing wrong with challenging assumptions.