- A practical synthesis of 5-lipoxygenase inhibitor MK-0633
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Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).
- Gosselin, Francis,Britton, Robert A.,Davies, Ian W.,Dolman, Sarah J.,Gauvreau, Danny,Hoerrner, R. Scott,Hughes, Gregory,Janey, Jacob,Lau, Stephen,Molinaro, Carmela,Nadeau, Christian,Oshea, Paul D.,Palucki, Michael,Sidler, Rick
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experimental part
p. 4154 - 4160
(2010/09/09)
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- The discovery of setileuton, a potent and selective 5-lipoxygenase inhibitor
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The discovery of novel and selective inhibitors of human 5-lipoxygenase (5-LO) is described. These compounds are potent, orally bioavailable, and active at inhibiting leukotriene biosynthesis in vivo in a dog PK/PD model. A major focus of the optimization
- Ducharme, Yves,Blouin, Marc,Brideau, Christine,Chateauneuf, Anne,Gareau, Yves,Grimm, Erich L.,Juteau, Helene,Laliberte, Sebastien,MacKay, Bruce,Masse, Frederic,Ouellet, Marc,Salem, Myriam,Styhler, Angela,Friesen, Richard W.
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scheme or table
p. 170 - 174
(2010/10/21)
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- THIADIAZOLE SUBSTITUTED COUMARIN DERIVATIVES AND THEIR USE AS LEUKOTRIENE BIOSYNTHESIS INHIBITOR
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The instant invention provides compounds of Formula (Ia) which are leukotriene biosynthesis inhibitors, wherein X is O or S, Y is O, S, -NR6-CHR7- or -NR8-C(O)- and A is selected from 5-membered aromatic heterocyclic ring, 6-membered aromatic heterocyclic ring, naphthelenic or heterobicyclic aromatic ring system, phenyl and benzyl. A is optionally mono- or disubstituted. Compounds of Formula (Ia) are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.
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Page/Page column 9; 43
(2008/06/13)
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