Abstract
A new solid-phase synthesis for ET receptor antagonists suitable for automation is presented. A support bound 2-hydroxybutyric acid derivative was converted to the corresponding ether derivatives using 4-halo-2-methylsulfonylpyrimidines. Subsequent Suzuki coupling with various aryl boronic acids gave the desired antagonists in good yields and purities. Highly potent antagonists with excellent selectivity for ET(A) were obtained.
MeSH terms
-
Animals
-
Butyrates / chemical synthesis*
-
Butyrates / pharmacology
-
CHO Cells
-
Combinatorial Chemistry Techniques
-
Cricetinae
-
Endothelin Receptor Antagonists*
-
Endothelin-1 / metabolism
-
Humans
-
Protein Binding
-
Pyrimidines / chemical synthesis*
-
Pyrimidines / pharmacology
-
Radioimmunoassay
-
Receptors, Endothelin / genetics
-
Receptors, Endothelin / metabolism
-
Resins, Synthetic
-
Structure-Activity Relationship
-
Transfection
Substances
-
Butyrates
-
Endothelin Receptor Antagonists
-
Endothelin-1
-
Pyrimidines
-
Receptors, Endothelin
-
Resins, Synthetic