SR3335 Chemical Properties

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

insoluble in H2O; ≥87.4 mg/mL in EtOH; ≥88.8 mg/mL in DMSO

form 

solid

color 

White to off-white

InChI

InChI=1S/C13H9F6NO3S2/c14-12(15,16)11(21,13(17,18)19)8-3-5-9(6-4-8)20-25(22,23)10-2-1-7-24-10/h1-7,20-21H

InChIKey

LZWUNZRMANFRAO-UHFFFAOYSA-N

SMILES

C1(S(NC2=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C=C2)(=O)=O)SC=CC=1

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

SR3335 Usage And Synthesis

Description

The retinoic acid receptor-related receptors (RORs) are orphan nuclear receptors with diverse putative roles. SR 3335 is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (K_i = 220 nM) and inhibiting constitutive transactivation activity (IC₅₀ = 480 nM). It is without effect on RORβ, RORγ, farnesoid X receptor, or liver X receptor α. SR 3335 evokes RORα-dependent effects both in vitro and in vivo, altering gene expression as well as gluconeogenesis.

Uses

SR3335 (ML 176) is a selective RORα inverse agonist that directly binds to RORα with a Ki of 220 nM[1][2].

Definition

ChEBI: N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-thiophenesulfonamide is a sulfonamide.

Synthesis

Under argon protection, 4-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)aniline (A) (1.5 M THF solution, 128 μL, 0.193 mmol) was dissolved in acetone (643 μL). Subsequently, 2,6-dimethylpyridine (29 μL, 0.251 mmol) and 2-thiophenesulfonyl chloride (0.193 mmol) were added sequentially and the reaction was carried out at room temperature. The reaction mixture was heated to 80 °C for 1 day. After completion of the reaction, it was cooled to room temperature and diluted with ethyl acetate (EtOAc) and saturated sodium bicarbonate (NaHCO3) solution. The aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated. The crude product was purified by silica gel column chromatography using hexane/ethyl acetate (7/3) as eluent to afford the target product N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-thiophene-sulfonamide (SR3335) as a white powder in 48 mg (62% yield). The compound has a CAS number of 2937-53-05-6 and is known in the literature and commercially available.

in vivo

target

RORα

References

[1] Kumar N, et al. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist. ACS Chem Biol. 2011 Mar 18;6(3):218-22. DOI:10.1021/cb1002762
[2] Rajput C, et al. RORα-dependent type 2 innate lymphoid cells are required and sufficient for mucous metaplasia in immature mice. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L983-L993. DOI:10.1152/ajplung.00368.2016