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Merck
  • 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.

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.

Journal of medicinal chemistry (2010-07-10)
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
PMID20614889
RÉSUMÉ

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.