A stereoselective approach to peptidomimetic BACE1 inhibitors

作者：Butini Stefania; Gabellieri Emanuele; Brindisi Margherita; Giovani Simone; Maramai Samuele; Kshirsagar Giridhar; Guarino Egeria; Brogi Simone; La Pietra Valeria; Giustiniano Mariateresa; Marinelli Luciana; Novellino Ettore; Campiani Giuseppe^*; Cappelli Andrea; Gemma Sandra

来源：European Journal of Medicinal Chemistry, 2013, 70: 233-247.

DOI：10.1016/j.ejmech.2013.09.056

• BACE1
• Inhibitors
• Benzodiazepines
• Alzheimer%26apos
• s disease
• Peptidomimetics

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.

• 出版日期2013-12