α-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases

KM Orrling, MR Marzahn, H Gutiérrez-de-Terán…

Index: Orrling, Kristina M.; Marzahn, Melissa R.; Gutierrez-de-Teran, Hugo; Aqvist, Johan; Dunn, Ben M.; Larhed, Mats Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 16 p. 5933 - 5949

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Citation Number: 24

Abstract

The impact of moving the P1 side-chain from the β-position to the α-position in norstatine- containing plasmepsin inhibitors was investigated, generating two new classes of tertiary alcohol-comprising α-benzylnorstatines and α-phenylnorstatines. Twelve α-substituted norstatines were designed, synthesized and evaluated for their inhibitory potencies against plasmepsin II and the plasmepsin IV orthologues (PM4) present in the digestive vacuole of ...