Biphenyl C-cyclopropylalkylamides: New scaffolds for targeting estrogen receptor beta.
The C-cyclopropylalkylamide scaffold was previously identified as a new structural framework for antiestrogens. A second generation library provided three compounds that bind estrogen receptor (ER)alpha. Further screening of this library identified an ERbeta hit and inspired another round of SAR. A new focused library was tested for binding to the ERs, and for effects on the growth of breast cancer cell lines and protein levels of common cell cycle regulators.
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Miranda J
MJ
Sarachine
Jelena M
JM
Janjic
Peter
P
Wipf
Billy W
BW
Day
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D047629:Estrogen Receptor beta / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008956:Models, Chemical; D011485:Protein Binding; D020033:Protein Isoforms; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D047629:Estrogen Receptor beta; D008024:Ligands; D020033:Protein Isoforms