(A) Reagents and conditions:
(a) 2-chloro-1,3,2-dioxaphospholane 2-oxide, TEA, toluene, 23 °C;
4 h; (b) trimethylamine, MeCN, 90 °C, 16 h; (c) conc. aq. HCl,
MeCN, 23 °C; 10 min. 12–49% over three steps and after
purification by preparative HPLC. (B) Luciferase reporter assay demonstrating
ligand efficacy, each bar represents activity at a different concentration
of designated compound, from right to left: 0.003, 0.03, 0.3, 1.0,
3.0, 10, and 30 μM. Represented as a measure of fold increase
in activity over vehicle. (C) Overlay of DLPC and RJW100 in LRH-1
LBD. Number of atoms in linker is counted between the 6HP core and
key PC binding element.