Science Concentrates
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Carfilzomib linked to higher cardiovascular risks Cancer drug increases risk of cardiac problems twofold Multiple myeloma is an incurable type of blood cell cancer. Two decades ago, people diagnosed with the disease lived for about 3–4 years. Now, thanks to new drugs including the protease inhibitor carfilzomib, those affected can survive for 10–20 years. However, since its approval by the U.S. Food & Drug Administration in 2012, people taking carfilzomib have experienced cardiac side effects, as noted on the drug’s labeling, but the risk of developing these conditions hasn’t been well defined. A new analysis of data from two dozen carfilzomib clinical trials has determined the incidence of adverse cadiac events such as heart failure, high blood pressure,
reduced blood flow, and irregular heartbeat (JAMA Oncol. 2017, DOI: 101001/ jamaoncol.2017.4519). The researchers, led by Adam Waxman of the University of Pennsylvania, found that 18% of carfilzomib-treated patients experienced at least one of these events, with 8% experiencing severe to life-threatening events. In three of the large, randomized trials, compared to people with myeloma not taking the drug, those taking carfilzomib were twice as likely to suffer from a cardiac event. Treating patients with severe diseases like multiple myeloma requires a constant balance between risks and benefits, says C.
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Carfilzomib Ola Landgren, an oncologist at Memorial Sloan Kettering Cancer Center, and unfortunately, all current treatments for the disease are associated with serious side effects such as pain, numbness, and organ failure. He points out that survival data were not presented in the new analysis as they were in two recent large clinical trials showing that people receiving combination treatments including carfilzomib lived up to eight months longer than those treated with other drugs. Carfilzomib’s high efficacy cannot be understated, Waxman says. He hopes the study will help inform patient-doctor discussions and push them to look for early signs of cardiac conditions. Some of these cardiovasular conditions may be reversible if patients stop taking the drug, and others like hypertension can be managed with medication.—TIEN NGUYEN
CATALYSIS
Sulfones expand the reach of radical cross-couplings New reagents offer streamlined synthesis of valuable fluorinated products two aryl partners, this type of cross-couCross-coupling reactions, wherein a pling is particularly well-suited for threadcatalyst brings together molecular parting together aryl and alkyl partners. ners to forge a new bond, are powerful With the help of a nickel catalyst and transformations that are among the most used tools in synthesis. For decades, researchers have Nickel mined this area of chemistry, OR catalyst O O developing methods for a lita+ S N ny of coupling partners. Now ClZn F F chemists have found a novel, F F N N N and valuable, pairing. R = tert-Butyldimethylsilyl bipyridine ligand, the reaction A team of researchers couples arylzinc compounds led by Phil Baran at Scripps with special alkylsulfone reagents. The Research Institute, California, has introresearchers demonstrated the scope of the duced alkylsulfones as coupling partners reaction with more than 60 examples confor radical cross-coupling reactions, protaining a variety of substitution patterns viding access to fluorinated structures and by synthesizing biologically relevant that would be cumbersome to make with molecules to highlight the shortened syntypical alkyl coupling partners (ChemRxiv thetic routes enabled by the technique. 2017, DOI: 10.26434/chemrxiv.5715106.v1). Notably, the sulfone reagents let reWhereas classic cross-couplings conjoin
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C&EN | CEN.ACS.ORG | JANUARY 8, 2018
searchers directly install fluorine atoms at the alkyl coupling site, whereas previously chemists would have had to run difficult deoxyfluorination reactions to make the requisite fluorinated coupling partner, says Scott Denmark of the University of Illinois, Urbana-Champaign. “The unique reactivity of the N-phenyltriazolylsulfones is surpassed only by their practicality as bench stable OR and odorless, crystalline compounds,” he says. “There is no doubt that this work is going to be game-changing and illustrates that there is still much to do in the field of cross-coupling,” say Cathleen Crudden of Queen’s University in Ontario and Masakazu Nambo of the Institute of Transformative Bio-Molecules at Nagoya University. The authors declined to speak with C&EN except to confirm the scientific accuracy of our reporting as per the embargo policies of the journal where they have submitted their manuscript.—TIEN NGUYEN
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