1.
Bioorg Med Chem Lett
; 16(6): 1574-8, 2006 Mar 15.
Article
in English
| MEDLINE
| ID: mdl-16386905
ABSTRACT
High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design.
Subject(s)
Enzyme Inhibitors/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Sulfonic Acids/pharmacology , Tetrahydroisoquinolines/chemistry , Binding Sites , Binding, Competitive , Crystallography, X-Ray , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Ligands , Models, Molecular , Molecular Mimicry , Phosphotyrosine/metabolism , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases/chemistry , Protein Tyrosine Phosphatases/metabolism , Structure-Activity Relationship , Sulfonic Acids/chemical synthesis , Sulfonic Acids/chemistry , src Homology Domains
2.
Bioorg Med Chem Lett
; 16(16): 4252-6, 2006 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-16759857
ABSTRACT
The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.