Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells. © 2013 Elsevier Masson SAS. All rights reserved.
Butini, S., Gabellieri, E., Brindisi, M., Giovani, S., Maramai, S., Kshirsagar, G., et al. (2013). A stereoselective approach to peptidomimetic BACE1 inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 70, 233-247 [10.1016/j.ejmech.2013.09.056].
A stereoselective approach to peptidomimetic BACE1 inhibitors
Butini, Stefania;Maramai, Samuele;Campiani, Giuseppe;Cappelli, Andrea;Gemma, Sandra
2013-01-01
Abstract
Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells. © 2013 Elsevier Masson SAS. All rights reserved.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/45618
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo