The Sweet Science

Hello, amine equivalent!
Source: Cumberland Packing Grp.

No, not boxing . . .chemistry!

From a fresh Org. Lett. ASAP, courtesy of the Amgen Process group, comes the 2-amination of some 3,5-disubstituted pyridine N-oxides. The group wants to add in an ammonia surrogate, but faces low conversions and poor regioselectivities (2- vs. 6-) with "standard" literature conditions (excess tert-butylamine, tosic anhydride). Substantial gains occur with a switch to Hunig's base and TsCl, but they need to find a bulky, electron-poor nitrogen source. Since we're potentially talking kilos here, price and availability become major considerations.

So what did the researchers choose as their "N" source? Saccharin. Yup, the artificial sweetener from the pink packets, used on process scale. Saccharin beat out many other "Gabriel-type" protected amines (phthalimide, Boc phosphoramidate, etc.), and you can't beat the price: about $5 / kilo. Under optimized conditions, the group saw yields from 21-97%, and product ratios of ~28:1. Better still, acidic hydrolysis (HCl, 80 degrees) frees up the 2-aminopyridine compounds, most of which are crystalline solids.

Pretty sweet synthesis.

What Do You Call Yourselves?

In the "hot-potato" game of Pharma jobs, it's not uncommon to work with a whole new cast of people every 5 years or so. I recall one such summer, where I watched the director and two lead chemists change around in just 3 months!

"Hi, I'm a GSKer."
"Really? I'm Ex-BMS!"

As you mix and match with refugees from layoffs, mergers, or plant closures, you encounter chemists from many different backgrounds. Perhaps they came from a rigid corporate hierarchy, or perhaps they were "pseudo-academics." Maybe they had legions of secretaries and associates, or maybe they were "armies of one" at a small start-up. But one thing everyone has?


A cute euphemism for where they used to work.


The Old "Ex-" (Most common): Ex-Pfizer, Ex-Merck, Ex-Lilly, Ex-BMS.


"-Ers": DuPonters, Merckers, GSKers, Genentechers*


"-Ites": Amgenites, Pfizerites


Engineers: Dow.


Geography Quiz: Sometimes, chemists will tell you they're from Nutley, Wilmington, or La Jolla, and expect you to intuit their former employers.


"Initials Only" Club: J&J, BASF, B-I, AZ.


Readers, I must be missing several. Have you heard any good ones?


Update, 3/8, 2:35AM - Chemjobber suggests "Pfizer alumni," and a Twitter respondent says the preferred internal term is "colleague."

An anonymous commenter suggests "BioGoners" for Ex-Biogen employees.


*(Yes, I checked all of these out on Google, and all have >150 hits, except "Genentechers" (76), which I usually hear via FiercePharma)

Osteoporitic Mice in Space

Clinical trials will have one last hurrah on the Final Frontier: According to a July 5 press release from Amgen and UCB Pharma, the last flight of the space shuttle program (STS-135 on Shuttle Atlantis) will carry mice receiving a sclerostin antibody to counter bone density loss. Mild osteoporosis (bone loss) and muscle atrophy are nothing new to astronauts (or cosmonauts, taikonauts, etc.), whose bodies change due to lack of normal gravity and from "skeletal disuse" brought on by insufficient exercise in spacecraft - you can't easily jog a mile when your track is 122.17 feet long.

I hadn't heard about UCB Pharma until this press release, although it's surprising, given that they have nearly 9,000 people across 40 countries! UCB proudly proclaims three (3) core products: Cimzia (certolizumab), Vimpat (lacosamide), and Neupro (rotigotine). Cimzia, an anti-inflammatory monoclonal antibody, comes with a catch: it's marketed in Europe for rheumatoid arthritis, but in the US, it's exclusively marketed for Crohn's, a bowel disorder. The other two are more "small-molecule" (and thus up my alley).  Lacosamide is a simple benzyl- and acetyl-protected O-methylserine used to treat epileptic and neuropathic pain. Hmm....a small peptide affecting the brain...wonder if it'll be Scheduled?  You betcha.

Rotigotine, a chiral (S-enantiomer) tetrahydronaphthylphenol with a stapled-on thiophenylamine, has been approved for Parkinson's and RLS.  Its story is equally convoluted: the molecule was originally developed by Aderis Pharma, which used to be Discovery Pharma. As Aderis, it was acquired by Schwarz pharma in 2005, and Schwarz as a whole acquired by UCB a few years later.  Got that?  Four companies, one molecule, roughly twelve years. 

Aside from these products, UCB's cash cow is Keppra (levetiracetam, for neropathic pain) and several generics, among them Zyrtec (allergies) and omeprazole (heartburn and GERD).  Their total haul for all meds? 2.8 billion Euros / year in net sales.

Update (July 30, 7:25PM) - Phew! Commenter gippgig spurs me to make some (important) changes to the (previously incorrect) drug structures. I've also changed the description of lacosamide from "homoserine" to "O-methylserine."