1.
Bioorg Med Chem Lett
; 27(11): 2629-2633, 2017 06 01.
Article
in English
| MEDLINE
| ID: mdl-28462834
ABSTRACT
Using fragment based and structure based drug discovery strategies a series of novel Sortilin inhibitors has been identified. The inhibitors are based on the N-substituted 1,2,3-triazol-4-one/ol heterocyclic template. X-ray crystallography shows that the 1,2,3-triazol-4-one/ol acts as a carboxylic acid isostere, making a bi-dentate interaction with an arginine residue of Sortilin, an interaction which has not been previously characterised for this heterocycle.
Subject(s)
Adaptor Proteins, Vesicular Transport/antagonists & inhibitors , Triazoles/chemistry , Adaptor Proteins, Vesicular Transport/metabolism , Binding Sites , Crystallography, X-Ray , Drug Design , Humans , Inhibitory Concentration 50 , Molecular Dynamics Simulation , Protein Structure, Tertiary , Structure-Activity Relationship , Triazoles/metabolism
2.
Bioorg Med Chem Lett
; 24(1): 177-80, 2014 Jan 01.
Article
in English
| MEDLINE
| ID: mdl-24355129
ABSTRACT
The identification of the novel, selective, orally bioavailable Sortilin inhibitor AF38469 is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.
