2. Academic Validation
  3. 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

  • J Med Chem. 2010 Aug 12;53(15):5801-12. doi: 10.1021/jm1005429.
Simon E Ward 1,  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
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. simon.e.ward@gsk.com
PMID: 20614889 DOI: 10.1021/jm1005429
Abstract

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.

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