Abstract
A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.
MeSH terms
-
Animals
-
Dihydroorotate Dehydrogenase
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Hydroxylamine
-
Immunosuppressive Agents / chemical synthesis*
-
Immunosuppressive Agents / chemistry
-
Immunosuppressive Agents / pharmacology
-
Indicators and Reagents
-
Isothiocyanates / chemical synthesis*
-
Isothiocyanates / chemistry
-
Isothiocyanates / pharmacology
-
Isoxazoles / chemical synthesis*
-
Isoxazoles / chemistry
-
Isoxazoles / pharmacology
-
Leflunomide
-
Lymphocyte Culture Test, Mixed
-
Lymphocytes / drug effects
-
Lymphocytes / immunology
-
Mice
-
Molecular Structure
-
Oxidoreductases / antagonists & inhibitors
-
Oxidoreductases Acting on CH-CH Group Donors*
-
Phenylacetates / chemistry
-
Recombinant Proteins / antagonists & inhibitors
-
Spectrometry, Mass, Fast Atom Bombardment
-
Structure-Activity Relationship
Substances
-
Dihydroorotate Dehydrogenase
-
Enzyme Inhibitors
-
Immunosuppressive Agents
-
Indicators and Reagents
-
Isothiocyanates
-
Isoxazoles
-
Phenylacetates
-
Recombinant Proteins
-
Hydroxylamine
-
Oxidoreductases
-
Oxidoreductases Acting on CH-CH Group Donors
-
Leflunomide