Arcyriarubin A

Bisindolylmaleimide IV (Arcyriarubin A) is a potent protein kinase C (PKC) inhibitor, with IC50s ranging from 0.1 to 0.55 μM. Bisindolylmaleimide IV also inhibits PKA (IC50=3.1-11.8μM)[1]. Bisindolylmaleimide IV is a potent, selective inhibitor of human cytomegalovirus (HCMV) replication in cell culture with an IC50 of 0.2 μM[2].

3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione is a member of indoles and a member of maleimides.

A. Chemical Examples; 3, 4-Di-(1 H-indol-3-yl)pyrrole-2, 5-dione (Compound 1); Potassium tert-butoxide (0.976 g, 8.7 mmol) was added to a stirred suspension of (1 H-indol-3-yl)acetamide (0.5 g, 2.8 mmol) and methyl 3-indolylglyoxylate (0.650, 3.15 mmol) in anhydrous tetrahydrofuran (15 ml), under argon at -10°C. After 15 minutes the resultant dark red solution was allowed to warm to 20°C over 3.5 hours. Concentrated hydrochloric acid (2ml) was added with cooling, and the orange-red precipitate then dissolved in ethyl acetate by stirring overnight. The organic phase was washed with water and brine, dried (magnesium sulphate) and evaporated to give the title compound as red crystals (0.780 g, 80.2percent yield), mp 234°C. A three-necked flask equipped with a magnetic stirrer and two addition funnels was charged with indole (10.1 g, 0.086 mol) and 100 mL of diethyl ether. Oxalyl chloride (7.3 mL, 0.086 mol) was added dropwise to the solution at 0 °C under nitrogen in 0.5 h. Yellow precipitate were formed and the reaction mixture was stirred for another 0.5 h. The reaction mixture was cooled to -70 °C by dry-ice, then sodium methylate (25 percent solution in methanol, 37.3 g, 0.173 mol) was added dropwise to the reaction mixture in 1 h. After that the reaction mixture was warmed to 0 °C and 50 mL of water was added. The precipitate were filtered, washed with water several times, and then dried at 60 °C under vacuum. The product of methyl indolyl-3- glyoxylate was obtained as a yellow powder and used without further purification. Yield 90 percent. A three-necked flask equipped with a magnetic stirrer and an addition funnel was charged with 3-indoleacetamide (8.0 g, 0.046 mol), methyl indolyl-3-glyoxylate (10.0 g, 0.049 mol) and 80 mL of tetrahydrofuran. A solution of potassium tert-butoxide (15.2 g, 0.135 mol) in 130 mL of tetrahydrofuran was added dropwise to the reaction mixture at 0 °C under nitrogen in 1.5 h. Then the reaction mixture was warmed to room temperature and stirred for 3 h. A solution of Hydrochloric acid (35 percent in water, 64 mL) was added dropwise to the reaction mixture in 1 h. Then 200 mL of ethyl acetate and 100 mL of water were added and stirred for dissolving. The organic phase was separated, washed with water several times until neutral, and then washed with brine once, dried over anhydrous sodium sulfate. The sodium sulfate was filtered and the solution was concentrated. The product was crystallized by adding a 1:1 (v/v) mixture of ethyl acetate and n-hexane dropwise to the concentrated solution at 50~60 °C. The pure product of 3, 4-bisindolylmaleimide was obtained as a red crystal.Take indole 2.34 g (0.02 mol), 3_ (indole_3) - maleimide 2.12g (0.01 mol), palladium acetate 0.11g(0.0005 mol) and copper acetate 2.72 g (0, 015 mol) were added to a 100 mL round bottom flask, DMSO 20 mL and DMF 10mL, heated to 80 ° C and stirred for 18h, the reaction completed, add water 50mL, Stir for 5 minutes and extract with ethyl acetate, Organic phase dry, columnObtained as a red solid2.51 g of 3, 4-bis (indole-3) -maleimide in 77percent yieldTetrahydrofuran (80mL), magnesium turnings (80.25 g, 0.33 moles) and iodine (0.5 g) were charged and stirred in a reaction flask equipped with mechanical stirrer, thermometer pocket, heating mantle, condenser, 500 mL addition funnel and nitrogen inlet. Slowly, ethyl bromide solution (30 mL, 0.40 moles) was added over one hour, maintaining the temperature below 40 °C. the reaction mixture was further stirred at the mass temperature of 30-40 °C, for another 30 minutes. Substituted indole (38.8 g, 0.333 moles) dissolved in toluene (81 mL) was charged to the addition funnel and was added dropwise over next one hour at temperature of 30- 40 °C. A solution of dichloro-N-methylmaleimide (20.05 g, 0.1114 moles) in toluene (150 mL) was prepared and added slowly, during which time a dark heterogenous mixture resulted. The mixture was heated to reflux (temperature = 110 °C) for one hour and monitored by TLC till the completion of the reaction (mobile phase: Chloroform : ethyl acetate = 6 : 1). The reaction mixture was cooled to 20-30 °C. 20 percent aqueous solution of citric acid (200 mL) slowly, at temperature below 5 °C, in one hour. The slurry was further stirred at 0 °C for 30 minutes. The red colored solid separates out. The product was isolated by filtration, rinsed with water and toluene, then dried in air. 28. 7 g (69.5 percent) of product was obtained, melting range: 280 °C (DSC), H. P. L. C. purity = 98.7 percent. If desired, the above product can be further recrystallised from acetone to obtain the PHARMACEUTICALLY ACCEPTABLE purity of more than 99. 5 percent (yield = 65 percent overall yield).

Molecular Weight:327.3
XLogP3:2.8
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:327.100776666
Monoisotopic Mass:327.100776666
Topological Polar Surface Area:77.8
Heavy Atom Count:25
Complexity:576
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes