Anthranillic acid amides and derivatives thereof as cosmetic and pharmaceutical active compounds

#The present invention relates to specific uses of compounds of the Formula 1 or of mixtures of two or more different compounds of the Formula 1.

#The invention also relates to selected compounds of the Formula 1 that were not known hitherto.

#A first aspect of the present invention relates to a use of a compound of the Formula 1 or of a mixture of two or more different compounds of the Formula 1 as a cosmetic agent for inhibiting the release of histamine from mast cells that is induced by the substance P or for the preparation of a medicament for the inhibition of the release of histamine from mast cells that is induced by the substance P.

#15 g (91 mmol) 4-hydroxycinnamic acid, 50 ml acetic anhydride and 0.5 ml pyridine are stirred at room temperature for 20 h. The mixture is poured into ice-water and the precipitated 4-acetoxycinnamic acid is separated off and dried (18 g). 15 g (77 mmol) 4-acetoxycinnamic acid are initially introduced and 15 g (100 mmol) thionyl chloride added dropwise. The mixture is then stirred for 1 h under reflux, the excess thionyl chloride is separated off by distillation and 50 ml toluene is added to the acid chloride. A solution of 7 g (51 mmol) anthranilic acid in 70 ml pyridine is added and the reaction mixture is stirred for 2 h at 90° C. After cooling, the reaction mixture is poured into ice-water and extracted with ethyl acetate, the organic phase is washed with water until neutral and the solvent is removed under vacuum. 300 g 10% sodium hydroxide solution is added to the residue and the mixture is stirred under reflux for 1-2 h. After cooling, the mixture is acidified with concentrated hydrochloric acid and extracted with ethyl acetate and the organic phase is washed with water until neutral and the solvent is removed under vacuum. The crude product (23 g) is recrystallised by repeated dissolving, with heating, in ethanol, cooling and precipitation by addition of water and is further purified by RP-18 medium-pressure chromatography (column: YMC ODS-AQ, eluent: methanol/water 50:50+0.5 ml acetic acid/l, λ280 nm) (yield: 1.1 g 10, purity: 95%).

#Spectroscopic data: 1H-NMR (300 MHz, D6 acetone): 8.91 (1H, dd, J=1.2 and 8.5 Hz), 8.14 (1H, dd, J=1.7 and 8.1 Hz), 7.67 (1H, d, J=15.4 Hz), 7.61 (1H, m), 7.60 (2H, d, J=8.7 Hz), 7.16 (1H, m), 6.92 (2H, d, J=8.7 Hz), 6.64 (1H, d, J=15.4 Hz). —13C-NMR (75.5 MHz, D6 acetone): 170.5 (s), 165.3 (s), 160.2 (s), 143.3 (s), 142.7 (d), 135.2 (d), 132.2 (d), 130.8 (2C, d), 127.3 (s), 123.0 (d), 120.9 (d), 119.8 (d), 116.6 (2C, d), 115.8 (s).

#140 mg N-(4-hydroxycinnamoyl)anthranilic acid (avenanthramide D, 10) are taken up in 20 ml ethanol and quantitatively hydrogenated with hydrogen in the presence of palladium (5% on active charcoal).