Biological Activity
c7280948 is a novel prmt1 inhibitor with ic50 value of 12.75 μm [1].protein arginine methyltransferase 1 (prmt1) is a histone methyltransferase specific for histone h4. prmt1 catalyzes the transfer of the methyl group from sam to the guanidine nitrogen atoms of arginine residues to produce monomethyl arginines (mma) and asymmetric dimethyl arginines (adma) [2].c7280948 is a novel prmt1 inhibitor. c7280948 interacts with aromatic residues at the hprmt1 substrate binding pocket (tyr 147 and tyr 160) [1]. c7280948 inhibited hprmt1 with ic50 value of 26.7 μm [3].
Synthesis
General procedure for the synthesis of 4-amino-N-phenethylbenzenesulfonamide from 4-nitro-N-phenethylbenzenesulfonamide: Concentrated hydrochloric acid (10-15 mL) was slowly added to a mixture of ethanol (10 mL) containing 4-nitro-N-phenethylbenzenesulfonamide or its analog (13a-q, 1.4 mmol, 1 equiv.) and tin particles (2-2.5 equiv.). The reaction mixture was refluxed for 3.5-6 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) until the feedstock completely disappeared. Upon completion of the reaction, the mixture was cooled to room temperature. Subsequently, 30% or 5 M aqueous sodium hydroxide solution was slowly added to the mixture until the reaction mixture became alkaline. The mixture was extracted with ethyl acetate (EA) or dichloromethane (DCM) and the organic layer was dried with anhydrous sodium sulfate (Na2SO4). The solvent was removed by evaporation under reduced pressure. If necessary, the product was purified by column chromatography. Using 13j (0.37 g, 1.2 mmol) as raw material, 4-amino-N-phenylethylbenzenesulfonamide (14j) was obtained as a yellow solid (0.39 g, 100% yield), which was ready to be used without further purification, according to the above described General Procedure B. The 1H NMR (DMSO-d6) data were as follows: δ 2.64 (2H, t, J = 7.7 Hz), δ 2.85 (2H, dt, J = 7.7, 5.8 Hz), 5.92 (2H, s), 6.60 (2H, d, J = 8.6 Hz), 7.12 (2H, d, J = 8.2 Hz), 7.20 (1H, t, J = 6.3 Hz), 7.26 (2H, t, J = 7.6 Hz), 7.40 (2H, d, J = 8.6 Hz).
References
[1]. heinke r, spannhoff a, meier r, et al. virtual screening and biological characterization of novel histone arginine methyltransferase prmt1 inhibitors. chemmedchem, 2009, 4(1): 69-77.
[2]. itoh y, suzuki t, miyata n. small-molecular modulators of cancer-associated epigenetic mechanisms. mol biosyst, 2013, 9(5): 873-896.
[3]. bissinger em, heinke r, spannhoff a, et al. acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hprmt1. bioorg med chem, 2011, 19(12): 3717-3731.
