Mp. 1H NMR and 13C NMR spectra were recorded on a
Mp. 1H NMR and 13C NMR spectra have been recorded on a Bruker Avance DPX500 spectrometer with operating CD40 Species frequencies of 500 and 125 MHz. All 13C NMR spectra were proton decoupled and all spectra were obtained in deuterated chloroform (CDCl3). Melting points have been performed in triplicate making use of Gallenkamp melting point apparatus (Loughborough, UK) and have been not corrected. High and low resolution MS (HRMS and LRMS) had been performed by the EPSRC National Mass Spectrometry Service, Swansea University, UK, using the stated ionisation strategy. Elemental analyses, performed by Medac Ltd. (Surrey, UK) werePharmaceutics 2013,applied to confirm compound purity (95 ). Calculated logP (ClogP) values had been determined using ChemDraw Ultra ten.0, CambridgeSoft, Cambridge, United states of america. two.1.1. Technique 1: Acid Chloride Synthesis Carboxylic acid derivatives of 4 or 5 were dissolved in dry tetrahydrofuran (wv 75 mg10 mL) and cooled to 0 below nitrogen. Thionyl chloride (five equiv.) was added slowly with stirring followed by three drops of dimethyl formamide. The mixture was allowed to warm to ambient temperature and was stirred overnight. Solvents have been removed below vacuum and the acid chloride product was made use of instantly with no further purification. 2.1.2. Process 2: Dithranol Di-Ester Co-Drug Synthesis 1 (500 mg, 1 equiv.) was dissolved in dry tetrahydrofuran (30 mL) and cooled with dry iceacetone for five minutes with constant agitation. Pyridine (0.27 mL, 1.5 equiv.) was added dropwise below nitrogen. The proper acid chloride (two equiv.) was dissolved in dry tetrahydrofuran (2 mL), cooled (dry iceacetone) for five min, then added gradually in to the mixture. The reaction was allowed to return to room temperature gradually and stirred overnight at space temperature. A single mole per liter HCl (50 mL) was added as well as the volatiles were removed by rotary evaporation. The mixture was extracted with dichloromethane (two 30 mL). The combined organic phases have been washed with saturated NaHCO3 DYRK2 drug answer (30 mL), dried more than MgSO4, and purified applying flash column chromatography utilizing dichloromethane 100 by way of to dichloromethane:ethyl acetate:petrol 13:1:6 as eluent. two.1.three. Method 3: Dithranol Mono-Ester Co-Drug Synthesis 1 (400 mg, 1 equiv.) was dissolved in ten mL anhydrous hexamethylphoramide (HMPA) and chilled to 0 under nitrogen. The suitable acid chloride (1 equiv.) was dissolved in dry HMPA (3 mL), cooled to 0 , and was added in dropwise style for the dithranol answer. The mixture was gradually warmed to ambient temperature and allowed to stir for five h. The mixture was poured into 300 mL water and extracted with dichloromethane (3 40 mL). The combined organic phases were washed with water (3 100 mL) followed by saturated NaHCO3 answer (100 mL). The organic phase was further washed with water (two one hundred mL) and dried over MgSO4, prior to purification making use of flash column chromatography. two.1.4. Dithranol Dimer Synthesis (three) Prepared in accordance with a published procedure [24], 1 (1 g) was dissolved in boiling acetic acid (100 mL), degassed and shielded from light. ten FeCl3 in acetic acid (12 mL) was added gradually. Water (five mL) was added and also the reaction product crystallized over a period of a few hours at room temperature. Re-crystallisation applying acetic acid afforded the desired product as a green powder (602 mg, 30 ). mp 24647 ; 1H NMR (CDCl3) 4.61 (s, 2H), 6.40 (d, 4H, J = 7.four Hz), 6.93 (d, 4H, J = 8.3 Hz), 7.41 (t, 4H, J = eight.0, 7.8 Hz), 11.73 (s, 4H, OH). 13C NMR (CDCl3) 56.3, 116.7, 11.