Abstract
AbstractAbstract:Rapastinel (GLYX‐13) is a natural amidated tetrapeptide (Thr‐Pro‐Pro‐Thr‐NH2)endowed with strong antidepressant property. Rapastinel shows considerable promise for treating drug‐resistant major depressive disorder (MDD), and is under clinical phase III development. Herein, we report the synthesis of a novel class of analogues of the potent antidepressant peptide drug rapastinel featuring rigid dipeptide scaffolds comprising proline (L/D) and amino thiophene carboxylates (Atc). Amino thiophene carboxylate is a conformationally constrained aromatic β‐amino acid, known to rigidify peptide backbones thereby limiting the conformational flexibility of peptides and improving proteolytic stability.
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