- Remote electronic control in the regioselective reduction of succinimides: A practical, scalable synthesis of EP4 antagonist MF-310
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(Chemical Equation Presented) A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a potential new treatment for chronic inflammation, is presented. The synthetic route provided MF-310 as its sodium salt in 10 steps and 17% overall yield from commercially available pyridine dicarboxylate 7. The key features of this sequence include a unique regioselective reduction of succinimide 2 controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid 3 via a Corey - Chaykovsky cyclopropanation, and a short synthesis of sulfonamide 5. 2009 American Chemical Society.
- Molinaro, Carmela,Gauvreau, Danny,Hughes, Gregory,Lau, Stephen,Lauzon, Sophie,Angelaud, Remy,O'Shea, Paul D.,Janey, Jacob,Palucki, Michael,Hoerrner, Scott R.,Raab, Conrad E.,Sidler, Rick R.,Belley, Michel,Han, Yongxin
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supporting information; experimental part
p. 6863 - 6866
(2009/12/30)
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- Structure-activity relationships and pharmacokinetic parameters of quinoline acylsulfonamides as potent and selective antagonists of the EP4 receptor
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A new series of EP4 antagonists based on a quinoline acylsulfonamide scaffold have been identified as part of our on-going efforts to develop treatments for chronic inflammation. These compounds show subnanomolar intrinsic binding potency towar
- Burch, Jason D.,Belley, Michel,Fortin, Rejean,Deschenes, Denis,Girard, Mario,Colucci, John,Farand, Julie,Therien, Alex G.,Mathieu, Marie-Claude,Denis, Danielle,Vigneault, Erika,Levesque, Jean-Francois,Gagne, Sebastien,Wrona, Mark,Xu, Daigen,Clark, Patsy,Rowland, Steve,Han, Yongxin
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p. 2048 - 2054
(2008/12/20)
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- QUINOLINE DERIVATIVES AS EP4 ANTAGONISTS
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The invention is directed to quinoline derivatives as prostaglandin E type receptor antagonists useful for the treatment of EP4 mediated diseases or conditions, such as acute and chronic pain, osteoarthritis, rheumatoid arthritis and cancer. The derivatives have the following structure of formula (I): wherein A and B represents either a nitrogen atom or a CH group with the proviso that they cannot both simultaneously be CH, Q can represent a nitrogen or a carbon atom, and Y and Z are either a nitrogen atom., a N(O) group or a C(R5) group. Pharmaceutical compositions comprising the derivatives of formula (I) are also included.
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