First synthesis of alpha-aminoalkyl-(N-substituted)thiocarbamoyl-phosphinates: inhibitors of aminopeptidase N (APN/CD13) with the new zinc-binding group.
OO-Di-trimethylsilyl esters of alpha-N-benzyloxycarbonylaminoalkylphosphinates (III) undergo triethylamine catalyzed addition to isothiocyanates to give after hydrolysis, a series of new alpha-aminoalkyl-(N-substituted)thiocarbamoyl-phosphinates. Thiocarbamoyl-phosphinate moiety can be included in the structures of the metalloproteinase inhibitors as the zinc-binding group and the new compounds reported here are good inhibitors of important aminopeptidase N(CD13) with IC(50) in range of 10.56-0.25 microM.
Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland.
Renata
R
Grzywa
Józef
J
Oleksyszyn
D001665:Binding Sites; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D020128:Inhibitory Concentration 50; D045726:Metalloproteases / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry*; D010721:Phosphinic Acids / Q000737:chemistry; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D010720:Phosphines; D010721:Phosphinic Acids; D045726:Metalloproteases; D018826:CD13 Antigens; D015032:Zinc