Solid-phase synthesis of endothelin receptor antagonists.
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.
BASF AG, D-67056 Ludwigshafen, Germany. udo.lange@abbott.com
Udo E W
UE
Lange
Wilfried M
WM
Braje
Willi
W
Amberg
Georg
G
Kettschau
D000818:Animals; D002087:Butyrates / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011863:Radioimmunoassay; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D012117:Resins, Synthetic; D013329:Structure-Activity Relationship; D014162:Transfection
D002087:Butyrates; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011743:Pyrimidines; D017466:Receptors, Endothelin; D012117:Resins, Synthetic