- Commercial synthesis of a pyrrolotriazine-fluoroindole intermediate to brivanib alaninate: Process development directed toward impurity control
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The development of a practical, commercial process for the preparation of 4-fluoro-2-methyl-indol-5-ol and its subsequent coupling with a pyrrolotriazine to form an advanced intermediate of the oncology therapy brivanib alaninate is described. A key aspect is the multikilogram-scale preparation of the fluoroindole intermediate from trifluoronitrobenzene and the subsequent coupling while achieving impurity minimalization. As brivanib alaninate is a high-dose drug, the synthesis of highquality API with low levels of impurities is critical.
- Pesti, Jaan A.,LaPorte, Thomas,Thornton, John E.,Spangler, Lori,Buono, Frederic,Crispino, Gerard,Gibson, Frank,Lobben, Paul,Papaioannou, Christos G.
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- Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38α MAP kinase inhibitors
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Pyrrolo[2,1-f][1,2,4]triazine based inhibitors of p38α have been prepared exploring functional group modifications at the C6 position. Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models o
- Dyckman, Alaric J.,Li, Tianle,Pitt, Sidney,Zhang, Rosemary,Shen, Ding Ren,McIntyre, Kim W.,Gillooly, Kathleen M.,Shuster, David J.,Doweyko, Arthur M.,Sack, John S.,Kish, Kevin,Kiefer, Susan E.,Newitt, John A.,Zhang, Hongjian,Marathe, Punit H.,McKinnon, Murray,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
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scheme or table
p. 4633 - 4637
(2011/09/15)
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- Aryl ketone pyrrolo-triazine compounds useful as kinase inhibitors
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Compounds having the formula (I), and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are surprisingly advantageous as p38 kinase inhibitors, wherein R3 is hydrogen, methyl, perfluoromethyl, methoxy, halogen, cyano, NH2
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