Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

Aya Nakagawa; Shigeyuki Uno; Makoto Makishima; Hiroyuki Miyachi; Yuichi Hashimoto

doi:10.1016/j.bmc.2008.05.016

Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

Bioorg Med Chem. 2008 Jul 15;16(14):7046-54. doi: 10.1016/j.bmc.2008.05.016. Epub 2008 May 10.

Authors

Aya Nakagawa¹, Shigeyuki Uno, Makoto Makishima, Hiroyuki Miyachi, Yuichi Hashimoto

Affiliation

¹ Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. [email protected]

PMID: 18586498
DOI: 10.1016/j.bmc.2008.05.016

Abstract

Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,4-dihydro-1,3-dioxoquinolin-2(1H)-yl)benzonitrile (DEPIQ-4CN) showed the most potent activity, with IC(50) values of 74-78nM in alkaline phosphatase activity and reporter gene assays.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase
Animals
CHO Cells
Cell Line, Tumor
Cricetinae
Cricetulus
Genes, Reporter
Humans
Inhibitory Concentration 50
Quinazolines / chemistry
Quinazolines / pharmacology*
Quinolines / chemistry
Quinolines / pharmacology*
Receptors, Progesterone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Quinazolines
Quinolines
Receptors, Progesterone
Alkaline Phosphatase