Discovery of substituted 8,9-dicarboxyldibenzo [2,3:5,6] bicyclo [5.2.0] nonan-4-ones with moderate binding affinity to the endothelin ETA and ETB receptors

Screening of our sample collection for novel structures with endothelin receptor (ETA and ETB) binding affinity, resulted in the discovery of structure I (R = H). This unique bicyclic diacid elicited modest affinity for both cloned human receptors (0.8 μM, ETA and 7.9 μM, ETB). Substitution at ‘R’ resulted in increased affinity for both receptors