Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 2

C V Walker; G Caravatti; A A Denholm; J Egerton; A Faessler; P Furet; C García-Echeverría; B Gay; E Irving; K Jones; A Lambert; N J Press; J Woods

doi:10.1016/s0960-894x(00)00476-5

Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 2

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2343-6. doi: 10.1016/s0960-894x(00)00476-5.

Authors

C V Walker¹, G Caravatti, A A Denholm, J Egerton, A Faessler, P Furet, C García-Echeverría, B Gay, E Irving, K Jones, A Lambert, N J Press, J Woods

Affiliation

¹ Novartis Horsham Research Centre, West Sussex, UK. clive.walker@pharma.novartis.com

PMID: 11055352
DOI: 10.1016/s0960-894x(00)00476-5

Abstract

A series of novel phosphinates, derived from 4-phosphonomethylphenylalanine, are described as isosteres of phosphotyrosine. Benzyl (or alkyl) phosphinomethylphenylalanine derivatives were prepared by alkylation of an amino acid P-H phosphinate.

MeSH terms

Adaptor Proteins, Signal Transducing*
Amino Acids
Drug Design
GRB2 Adaptor Protein
Molecular Structure
Phenylalanine / analogs & derivatives*
Phosphinic Acids / chemical synthesis*
Phosphinic Acids / chemistry
Phosphinic Acids / pharmacology
Phosphotyrosine / analogs & derivatives*
Phosphotyrosine / chemical synthesis
Phosphotyrosine / chemistry
Proteins / antagonists & inhibitors*
Proteins / chemistry*
Structure-Activity Relationship
src Homology Domains

Substances

Adaptor Proteins, Signal Transducing
Amino Acids
GRB2 Adaptor Protein
Phosphinic Acids
Proteins
4-phosphonomethylphenylalanine
Phosphotyrosine
Phenylalanine