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Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a Novel Clinical AMPA Receptor Positive Modulator

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journal contribution
posted on 12.08.2010, 00:00 by Simon E. Ward, Mark Harries, Laura Aldegheri, Daniele Andreotti, Stuart Ballantine, Benjamin D. Bax, Andrew J. Harris, Andy J. Harker, Jesper Lund, Rosemary Melarange, Anna Mingardi, Claudette Mookherjee, Julie Mosley, Marta Neve, Beatrice Oliosi, Roberto Profeta, Kathrine J. Smith, Paul W. Smith, Simone Spada, Kevin M. Thewlis, Shahnaz P. Yusaf
A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.