First synthesis of alpha-aminoalkyl-(N-substituted)thiocarbamoyl-phosphinates: inhibitors of aminopeptidase N (APN/CD13) with the new zinc-binding group

Renata Grzywa; Józef Oleksyszyn

doi:10.1016/j.bmcl.2008.05.050

First synthesis of alpha-aminoalkyl-(N-substituted)thiocarbamoyl-phosphinates: inhibitors of aminopeptidase N (APN/CD13) with the new zinc-binding group

Bioorg Med Chem Lett. 2008 Jul 1;18(13):3734-6. doi: 10.1016/j.bmcl.2008.05.050. Epub 2008 May 17.

Authors

Renata Grzywa¹, Józef Oleksyszyn

Affiliation

¹ Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland.

PMID: 18524593
DOI: 10.1016/j.bmcl.2008.05.050

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
CD13 Antigens / antagonists & inhibitors*
Chemistry, Pharmaceutical / methods*
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Humans
Hydroxamic Acids / chemistry
Inhibitory Concentration 50
Metalloproteases / chemistry
Models, Chemical
Molecular Structure
Phosphines / chemistry*
Phosphinic Acids / chemistry
Structure-Activity Relationship
Zinc / chemistry*

Substances

Enzyme Inhibitors
Hydroxamic Acids
Phosphines
Phosphinic Acids
Metalloproteases
CD13 Antigens
Zinc