140468-58-2Relevant articles and documents
α-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases
Orrling, Kristina M.,Marzahn, Melissa R.,Gutierrez-de-Teran, Hugo,Aqvist, Johan,Dunn, Ben M.,Larhed, Mats
experimental part, p. 5933 - 5949 (2009/12/24)
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-s
A Series of Potent HIV-1 Protease Inhibitors Containing a Hydroxyethyl Secondary Amine Transition State Isostere: Synthesis, Enzyme Inhibition, and Antiviral Activity
Tucker, Thomas J.,Lumma, William C.,Payne, Linda S.,Wai, Jenny M.,Solms, S. Jane de,et al.
, p. 2525 - 2533 (2007/10/02)
A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized.The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group.Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction.N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T-lymphoid cells.Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors.
