Ketomethylene analogues of phosphoryl dipeptides related to phosphoramidon: synthesis and inhibition of proteases.
Non-rhamnose-containing phosphoramidon analogues, in which the amide bond was replaced by the isosteric ketomethylene group, have been synthesized in order to stabilize these compounds to peptidase degradation. The key step in this synthesis was suitable alkylation of a 4-ketodiester, prepared from Z-Leu chloromethyl ketone and dimethyl malonate. The ketomethylene dipeptide derivatives P-Leu psi (COCH2)(RS)Xaa-OMe (Xaa = Trp, Phe) are good inhibitors of thermolysin, ACE and specially enkephalinase.
Gómez-Monterrey
I
I
Medicinal Chemistry Institute, Madrid, Spain.
González Muñiz
R
R
Pérez-Martín
C
C
López de Ceballos
M
M
Del Río
J
J
García-López
M T
MT
D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D004151:Dipeptides; D006020:Glycopeptides; D011480:Protease Inhibitors; C008890:phosphoramidon