1246525-60-9

SR 1078 is a selective agonist of RORα and RORγ that stimulates ROR transcriptional activity in HEK293 cell reporter assays.

sr1078 is an agonist of retinoic acid receptor-related orphan receptor (ror) rorα and rorγ with ic50 values of both 1-3 μm [1].rorα and rorγ are two members of nuclear receptor superfamily, which possesses a highly conserved dna-binding and a ligand-binding domain. these two receptors are considered to play important roles in the regulation of metabolism and the function of immune system [1].sr1078 is a selective rorα and rorγ agonist, which activate rorα and rorγ directed transcription via inducing conformational changes [1].sr1078 selectively targets on rorα and rorγ as an agonist but not on lxr and fxr [1]. it was shown that sr1078 was able to stimulate ror activity and subsequent ror-directed mrna expression. when hepg2 cells were treated with sr1078 for 24h, the ror directed reporter gene fg21 mrna level was increased by 3-fold, while another reporter gene g6pase was increased by 2-fold [1].in mouse model, i.p. injection of 10 mg/kg sr1078 for 1 hr resulted in 3.6 μm plasma concentration., and after 8 hr the concentration still sustained at 800 nm. i.p. injection of 10 mg/kg sr1078 for 2 hr resulted in significantly increased level of mrna of reporter gene g6pase and fg21 [1].

To a solution of dichloromethane (275 μL) containing 4-(hexafluoro-2-hydroxyisopropyl)aniline (1.5 M THF solution, 128 μL, 0.193 mmol) was added sequentially N,N-diisopropylethylamine (37 μL, 0.212 mmol) and 4-trifluoromethylbenzoyl chloride (30 μL, 0.193 mmol), protected by argon. The reaction mixture was stirred at room temperature for 8 h and then concentrated under reduced pressure. The crude product was purified directly by silica gel column chromatography with the eluent of hexane/ethyl acetate (8/2) to afford 59 mg (71% yield) of N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide (SR1078) as a white powder. Infrared spectrum (IR, cm-1): 3404, 3214, 1671, 1602, 1529, 1417, 1322, 1272, 1206, 1190, 1176, 1138, 1117, 1065, 1016, 973, 964, 948, 902, 857, 830, 765, 752, 737, 704, 692. 1H NMR. 692. 1H NMR (400 MHz, (CD3)2SO): δ 7.68 (d, J = 8.2 Hz, 2H), 7.89-7.96 (m, 4H), 8.16 (d, J = 8.2 Hz, 2H), 8.66 (s, 1H), 10.67 (s, 1H). 13C NMR (100 MHz, (CD3)2SO): δ 120.12 (2C), 125.4 (q, J = 4.0 Hz, 2C), 125.8, 123.3 (2C), 128.7 (2C), 131.5 (q, J = 31.9 Hz, 1C), 138.4, 140.4, 164.7. mass spectra (ES-): m/z = 430 (C17H10F9NO2-H+). Melting point: 169°C.

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[1] wang y et al. , identification of a synthetic agonist for the orphan nuclear receptors rorα and rorγ, sr1078. acs chem biol., 2010, 5(11): 1029-1034.