1307741-03-2Relevant academic research and scientific papers
Structure-activity relationship-guided development of retinoic acid receptor-related orphan receptor gamma (RORγ)-selective inverse agonists with a phenanthridin-6(5H)-one skeleton from a liver X receptor ligand
Nishiyama, Yuko,Nakamura, Masahiko,Misawa, Takashi,Nakagomi, Madoka,Makishima, Makoto,Ishikawa, Minoru,Hashimoto, Yuichi
, p. 2799 - 2808 (2014/05/06)
Retinoic acid receptor-related orphan receptors (RORs), which belong to the nuclear receptor superfamily, regulate many physiological processes, including hepatic gluconeogenesis, lipid metabolism, immune function and circadian rhythm. Since RORs resemble liver X receptors (LXRs) in the fold structure of their ligand-binding domains, we speculated that ROR-mediated transcription might be modulated by LXR ligands, in line with the multi-template hypothesis. Therefore, we screened our LXR ligand library for compounds with ROR ligand activity and identified a novel ROR ligand with a phenanthridin-6(5H)-one skeleton. Structure-activity relationship studies aimed at separating ROR inverse agonistic activity from LXR-agonistic activity enabled us to develop a series of ROR inverse agonists based on the phenanthridin-6(5H)-one skeleton, including a RORγ-selective inverse agonist.
Fused heterocyclic amido compounds as anti-hepatitis C virus agents
Aoyama, Hiroshi,Sugita, Kazuyuki,Nakamura, Masahiko,Aoyama, Atsushi,Salim, Mohammed T.A.,Okamoto, Mika,Baba, Masanori,Hashimoto, Yuichi
, p. 2675 - 2687 (2011/06/11)
We identified a fused heteroaromatic amido structure based on the phenanthridine skeleton as a superior scaffold for candidate drugs with potent anti-HCV activity. Among the compounds synthesized, a phenanthridine analogue with a 1,3-dioxolyl group (24) possessed the most potent anti-HCV activity (EC50 value: 50 nM), with acceptable cytotoxicity. The structural development and structure-activity relationships of these compounds are described.
