NEWS OF THE W EEK
CELGENE TO BUY PARTNER PHARMION ACQUISITION: $2.9 billion purchase will strengthen Celgene’s oncology pipeline
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EEKING TO BROADEN its portfolio of blood and
cancer therapies, Celgene has agreed to acquire Boulder, Colo.-based Pharmion for $2.9 billion. Celgene is a midsized drug company formed in 1986 after the merger of Celanese and American Hoechst. In 1998, the Summit, N.J., firm received FDA approval for a multiple myeloma treatment based on thalidomide, an insomnia and morning sickness drug that caused birth defects in the 1950s and ’60s. Celgene subsequently won approval for Revlimid, an analog of thalidomide, also for multiple myeloma. Pharmion is the firm’s first major acquisition. “The acquisition of Pharmion is an exceptional strategic fit that will exCELGENE/NEWSCOM
Starting with thalidomide in 1998, Celgene has expanded into a $900 million-ayear company.
SUPPORTED CROSS-METATHESIS SOLID-PHASE SYNTHESIS: Linker promotes effective alkene coupling
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A linker (red) provides the right distance between the solid support (blue) and the substrate’s (green) reactive olefin for efficient crossmetathesis.
LEFIN CROSS-METATHESIS, the coupling of two distinct alkenes, is a useful synthetic organic reaction, but it has only rarely been achieved on solid phase. Researchers have now found that proper spacing between the polymer support Cl and the tethered alkene makes the solid-phase reaction more feasible. Solid-phase synthesis is used to construct diverse small-molecule libraries in an automated fashion, allowO ing easy removal of by-products O and excess reagents from reaction mixtures. The finding could aid the use of olefin cross-metathesis in discovering comCl pounds with novel bioactivities. Kazunori Koide, assistant professor of chemistry at the University of Pittsburgh, and graduate student Amanda L. Garner found that increasing the distance between the polymer and the support-bound olefin in olefin cross-metathesis reactions leads to higher WWW.C E N- ONLI NE .ORG
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pand our role as a leader in hematology and oncology,” says Celgene CEO Sol J. Barer. The deal will bring Celgene several drugs and drug candidates, including Vidaza, approved in the U.S. for myelodysplastic syndromes (MDS), and a myeloma treatment that Pharmion is developing for Europe based on thalidomide licensed from Celgene. Pharmion has four products on the market and several in development that are focused on hematological and solid tumor cancers. Recent Phase II clinical trials demonstrated that Vidaza extended overall survival by 74% compared with conventional MDS regimes. Pharmion expects to apply for European approval of Vidaza for high-risk MDS before the end of the year. Pharmion’s thalidomide product is currently under review by the European Medicines Agency. The company expects a response by early 2008. Friedman, Billings, Ramsey Group, an investment banking and stock research firm, sees Pharmion as an ideal fit for Celgene that comes at a good price. “Celgene’s decision to acquire Pharmion was probably driven by the game-changing survival data on Vidaza in MDS,” FBR analyst James Reddoch wrote in a note to clients. He expects the deal to add $1 billion in annual sales by 2012, based on Pharmion’s current revenues and an estimate of $900 million in future Vidaza sales. The acquisition is expected to close by the second quarter of 2008.—RICK MULLIN
product yields (Org. Lett., DOI: 10.1021/ol702415x). To apply their findings to diverse substrates, Koide and Garner constructed a novel solid support by attaching a linker to a well-known polystyrene resin. Cross-metathesis of several alkene substrates proceeded in moderate to good yields on the team’s new polymer support but poorly on supports lacking a linker. But earlier studies of solid-phase metathesis by other groups show that increased linker length is beneficial only up to a point, Koide cautions. “If the linker is too long, two olefins bound to the solid support may reach each other and react” and form an undesired product, he says. Sequestering one of the reacting olefins on a solid support is one way to boost yields of desired coupling products while minimizing metathesis of one partner with itself, according to Helen E. Blackwell, assistant professor of chemistry at the University of Wisconsin, Madison. A rigorous study of solid-phase olefin cross-metathesis “has been warranted for many years,” she adds. The new method is “mild and should be straightforward to implement on various substrates,” Blackwell says. As an example, Garner and Koide implemented their new technology to perform a cross-metathesis reaction between a natural product substrate and a solid-supported epoxide. Koide next plans to build a library of highly functionalized compounds for biological studies.—CARMEN DRAHL
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