| Identification | Back Directory | [Name]
SR 1078 | [CAS]
1246525-60-9 | [Synonyms]
SR 1078
SR 1078; SR-1078
SR 1078 USP/EP/BP
SR1078;SR 1078;SR-1078
SR1078,N-[4-(2,2,2-TRIFLUORO-1-HYDROXY-1-TRIFLUOROMETHYL-ETHYL)-PHENYL]-4-TRIFLU
N-[4-(1,1,1,3,3,3-Hexafluoro-2-hydroxy-2-propanyl)phenyl]-4-(trifluoromethyl)benzamide
N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide
Benzamide, N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)-
SR1078,N-[4-(2,2,2-Trifluoro-1-hydroxy-1-trifluoroMethyl-ethyl)-phenyl]-4-trifluoroMethyl-benzaMide
N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide SR1078 | [Molecular Formula]
C17H10F9NO2 | [MDL Number]
MFCD18782737 | [MOL File]
1246525-60-9.mol | [Molecular Weight]
431.25 |
| Chemical Properties | Back Directory | [Melting point ]
169℃ | [Boiling point ]
362.9±42.0 °C(Predicted) | [density ]
1.527±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO, Methanol (Slightly) | [form ]
Solid | [pka]
9.21±0.15(Predicted) | [color ]
Off-White | [InChI]
1S/C17H10F9NO2/c18-15(19,20)11-3-1-9(2-4-11)13(28)27-12-7-5-10(6-8-12)14(29,16(21,22)23)17(24,25)26/h1-8,29H,(H,27,28) | [InChIKey]
DUXWIYXHHGNUJU-UHFFFAOYSA-N | [SMILES]
O=C(NC1=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C=C1)C2=CC=C(C=C2)C(F)(F)F |
| Hazard Information | Back Directory | [Uses]
SR 1078 is a selective agonist of RORα and RORγ that stimulates ROR transcriptional activity in HEK293 cell reporter assays. | [Biological Activity]
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]. | [Synthesis]
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. | [in vivo]
The pharmacokinetic properties of SR1078 are examined in mice and noted significant exposure. Plasma concentrations reach 3.6 μM 1h after a 10 mg/kg i.p. injection of SR1078 and sustained levels of above 800 nM even 8h after the single injection. These levels are sufficient to perform a proof-of-principle experiment to determine if SR1078 treatment would stimulate ROR target gene expression in an animal model. Mice are treated with SR1078 (10 mg/kg; i.p.) and 2h after the injection the livers are harvested and mRNA purified for assessment of G6Pase and FGF21 gene expression.T he expression of both FGF21 and G6Pase is significantly stimulated by SR1078 treatment vs. vehicle control[1].
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SR1078 (10 mg/kg; i.p.) shows a significant 25% reduction in repetitive grooming behavior in the BTBR mice[2]. | [storage]
Store at -20°C | [References]
[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. |
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LETOPHARM LIMITED
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+86-21-5821 5861 |
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www.letopharm.com |
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SPIRO PHARMA
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www.spiropharma.com.cn |
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