4-(3-pyridinyloxy)benzene-1-2-dicarbonitrile and Breast-Neoplasms

Aromatase inhibition is the new standard of care for estrogen receptor positive breast cancer and has also potential for treatment of other diseases such as endometriosis. Simple and readily available 3-pyridyl arylethers and 1-aryl pyrrolo[2,3-c]pyridines recapitulating the key pharmacophore elements of Letrozole (1) are described and their structure-activity relationships are discussed. Potent and ligand efficient leads such as compound 23 (IC(50)=59nM on aromatase) have been identified.

Topics: Antineoplastic Agents; Aromatase; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Models, Molecular; Pyridines; Pyrroles; Structure-Activity Relationship