TY - JOUR
T1 - Novel Nonsteroidal Progesterone Receptor (PR) Antagonists with a Phenanthridinone Skeleton
AU - Nishiyama, Yuko
AU - Mori, Shuichi
AU - Makishima, Makoto
AU - Fujii, Shinya
AU - Kagechika, Hiroyuki
AU - Hashimoto, Yuichi
AU - Ishikawa, Minoru
N1 - Funding Information:
The work described in this Letter was partially supported by Grants-in Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science (KAKENHI Grant No. 17H03996 (Y.H.), No. 17H03997 (S.F.), and No. 25293027 (M.I.)).
Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/7/12
Y1 - 2018/7/12
N2 - The progesterone receptor (PR) plays an important role in various physiological systems, including female reproduction and the central nervous system, and PR antagonists are thought to be effective not only as contraceptive agents and abortifacients but also in the treatment of various diseases, including hormone-dependent cancers and endometriosis. Here, we identified phenanthridin-6(5H)-one derivatives as a new class of PR antagonists and investigated their structure-activity relationships. Among the synthesized compounds, 37, 40, and 46 exhibited very potent PR antagonistic activity with high selectivity for PR over other nuclear receptors. These compounds are structurally distinct from other nonsteroidal PR antagonists, including cyanoaryl derivatives, and should be useful for further studies of the clinical utility of PR antagonists.
AB - The progesterone receptor (PR) plays an important role in various physiological systems, including female reproduction and the central nervous system, and PR antagonists are thought to be effective not only as contraceptive agents and abortifacients but also in the treatment of various diseases, including hormone-dependent cancers and endometriosis. Here, we identified phenanthridin-6(5H)-one derivatives as a new class of PR antagonists and investigated their structure-activity relationships. Among the synthesized compounds, 37, 40, and 46 exhibited very potent PR antagonistic activity with high selectivity for PR over other nuclear receptors. These compounds are structurally distinct from other nonsteroidal PR antagonists, including cyanoaryl derivatives, and should be useful for further studies of the clinical utility of PR antagonists.
KW - antagonist
KW - nonsteroid
KW - phenanthridinone
KW - Progesterone receptor
UR - http://www.scopus.com/inward/record.url?scp=85049238851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049238851&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.8b00058
DO - 10.1021/acsmedchemlett.8b00058
M3 - Article
AN - SCOPUS:85049238851
SN - 1948-5875
VL - 9
SP - 641
EP - 645
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 7
ER -
