Aiming at identifying new scaffolds for BACE-1 inhibition devoid of the pharmacokinetic drawbacks of peptide-like structures, we investigated a series of novel peptidomimetics based on a 1,4-benzodiazepine (BDZ) core 1a-h and their seco-analogues 2a-d. We herein discuss synthesis, molecular modeling and in vitro studies which, starting from 1a, led to the seco-analogues (R)-2c and (S)-2d endowed with BACE-1 inhibition properties in the micromolar range both on the isolated enzyme and in cellular studies. These data can encourage to pursue these analogues as hits for the development of a new series of BACE-1 inhibitors active on whole-cells.
Butini, S., Gabellieri, E., Brindisi, M., Casagni, A., Guarino, E., Huleatt, P.B., et al. (2013). Novel peptidomimetics as BACE-1 inhibitors: synthesis, molecular modeling, and biological studies. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 23(1), 85-89 [10.1016/j.bmcl.2012.11.011].
Novel peptidomimetics as BACE-1 inhibitors: synthesis, molecular modeling, and biological studies
Butini, Stefania;Gabellieri, Emanuele;Casagni, Alice;Guarino, Egeria;Huleatt, Paul B.;Relitti, Nicola;Campiani, Giuseppe;Gemma, Sandra
2013-01-01
Abstract
Aiming at identifying new scaffolds for BACE-1 inhibition devoid of the pharmacokinetic drawbacks of peptide-like structures, we investigated a series of novel peptidomimetics based on a 1,4-benzodiazepine (BDZ) core 1a-h and their seco-analogues 2a-d. We herein discuss synthesis, molecular modeling and in vitro studies which, starting from 1a, led to the seco-analogues (R)-2c and (S)-2d endowed with BACE-1 inhibition properties in the micromolar range both on the isolated enzyme and in cellular studies. These data can encourage to pursue these analogues as hits for the development of a new series of BACE-1 inhibitors active on whole-cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/43785
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