2. Academic Validation
  3. Cyclic sulfamide gamma-secretase inhibitors

Cyclic sulfamide gamma-secretase inhibitors

  • Bioorg Med Chem Lett. 2005 Oct 1;15(19):4212-6. doi: 10.1016/j.bmcl.2005.06.084.
Tim Sparey 1,  Dirk Beher,  Jonathan Best,  Mirlinda Biba,  José L Castro,  Earl Clarke,  Joanne Hannam,  Timothy Harrison,  Huw Lewis,  Andrew Madin,  Mark Shearman,  Bindi Sohal,  Nancy Tsou,  Christopher Welch,  Jonathan Wrigley
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. tim_sparey@merck.com
PMID: 16054361 DOI: 10.1016/j.bmcl.2005.06.084
Abstract

A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo gamma-secretase activity. One compound with subnanomolar activity elicited a reduction in brain Abeta40 after oral dosing in APP-YAC mice.

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