Synthesis of cyclic prodrugs of Aggrastat and its analogue with a modified phenylpropionic acid linker.
[structure: see text] The objective of this work was to synthesize cyclic prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an ester bond between the -COOH group of Aggrastat or its analogue and the phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and the -COOH group of the linker 3, respectively, as outlined in Scheme 4.
Song
Xiaoping
X
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
He
Henry T
HT
Siahaan
Teruna J
TJ
D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D010666:Phenylpropionates / Q000737:chemistry; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D010666:Phenylpropionates; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D014443:Tyrosine