Forskningsartikel2009Vetenskapligt granskad
Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S: Effect of sulfonamides P3 substituents on potency and selectivity
Ayesa, Susana; Lindquist, Charlotta; Agback, Tatiana; Benkestock, Kurt; Classon, Bjoern; Henderson, Ian; Hewitt, Ellen; Jansson, Katarina; Kallin, Anders; Sheppard, Dave; Samuelsson, Bertil
Sammanfattning
Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure-activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity pro. le and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K. (c) 2008 Elsevier Ltd. All rights reserved.
Nyckelord
Serin protease; Inhibitors; Cathepsin K; Cathepsin S; Reversible covalent inhibition
Publicerad i
Bioorganic and Medicinal Chemistry
2009, Volym: 17, nummer: 3, sidor: 1307-1324
Utgivare: PERGAMON-ELSEVIER SCIENCE LTD
UKÄ forskningsämne
Läkemedelskemi
Publikationens identifierare
DOI: https://doi.org/10.1016/j.bmc.2008.12.020
Permanent länk till denna sida (URI)
https://res.slu.se/id/publ/99467