title: New aromatase inhibitors from the 3-pyridyl arylether and 1-aryl pyrrolo[2,3-c]pyridine series.
abstract: 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.
authors.affiliation: Novartis Institutes for BioMedical Research, Global Discovery Chemistry Oncology, Postfach, CH-4002 Basel, Switzerland. frederic.stauffer@novartis.com
authors.forename: Frédéric
authors.initials: F
authors.lastname: Stauffer
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Andreas
authors.initials: A
authors.lastname: Floersheimer
authors.forename: Marc
authors.initials: M
authors.lastname: Lang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D006801:Humans; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D011725:Pyridines; D011758:Pyrroles; C475261:pyrrolo(3,2-c)pyridine; D001141:Aromatase