Bioorganic & Medicinal Chemistry Letters 2008-01-01

Sulfonamide derivatives of bridgehead substituted bicyclo[4.2.1]nonanes as gamma-secretase inhibitors.

Tim Sparey, Earl Clarke, Joanne Hannam, Timothy Harrison, Andrew Madin, Mark Shearman, Bindi Sohal

Index: Bioorg. Med. Chem. Lett. 18(1) , 375-9, (2008)

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Abstract

Bridgehead substituted derivatives of bicyclo[4.2.1]nonanes were synthesized and shown to be potent inhibitors of gamma-secretase. Two related series were synthesized to explore the SARs. More potent compounds were found in the non-benzofused series compared with the benzofused series. One compound from each series showed good exposure in the hepatic portal vein (HPV) following oral dosing to rats.