Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 2.
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.
Walker
C V
CV
Novartis Horsham Research Centre, West Sussex, UK. clive.walker@pharma.novartis.com
Caravatti
G
G
Denholm
A A
AA
Egerton
J
J
Faessler
A
A
Furet
P
P
García-Echeverría
C
C
Gay
B
B
Irving
E
E
Jones
K
K
Lambert
A
A
Press
N J
NJ
Woods
J
J
D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D015195:Drug Design; D051380:GRB2 Adaptor Protein; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives*; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019000:Phosphotyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D051380:GRB2 Adaptor Protein; D010721:Phosphinic Acids; D011506:Proteins; C083973:4-phosphonomethylphenylalanine; D019000:Phosphotyrosine; D010649:Phenylalanine