Synthetic analogs of xanthohumol for use in the prevention and​/or treatment of tumors

The present invention relates to novel synthetic analogs I [wherein: R1 and R2 are independently selected from the group consisting of H, Me, straight or branched C2-​10-​alkyl, straight or branched C2-​10-​alkenyl or -​alkadienyl, C4-​6-​cycloalkyl, C4-​6-​cycloalkenyl or -​alkadienyl, alkoxyalkyl, (un)​substituted benzyl; n is an integer ranging from I to 5;]​. [A is a mono- or bicyclic aryl, or an (non)​arom. heterocycle ring selected from the group consisting of pyrrole, pyrrolidine, 3-​pyrroline, 2H-​pyrrole, 2-​pyrroline, indole, isoindole, 3H-​indole, indolizine, indoline, carbazole, furan, benzofuran, isobenzofuran, 2H-​pyran, 4H-​pyran, benzo[b]​thiophene, thiophene, pyridine, piperidine, 4H-​quinolizine, isoquinoline, quinoline, tetrahydroquinoline, 1,​8-​naphthyridine, acridine, oxazole, isoxazole, benzoxazole, benzothiazole, isothiazole, thiazole, imidazole, 2-​imidazole, imidazolidine, tetrazole, 1,​2,​3-​triazole, 1,​2,​4-​triazole, 1,​2,​3-​oxadiazole, benzimidazole, purine, 1,​4-​dioxane, 1,​3-​dioxolane, 1,​3-​dithiane, 1,​4-​dithiane, 1,​3,​5-​trithiane, morpholine, thiomorpholine, phenothiazine, pyrazole, 2-​pyrazoline, pyrazolidine, quinazoline, cinnoline, pyrimidine, pyrazine, pteridine, phthalazine, 1,​2,​4-​triazine, 1,​3,​5-​triazine, pyridazine, piperazine, quinoxaline, phenazine, lH-​indazole;]​. [Wherein the substituents on ring A, independently from each other, are selected from the group consisting of H, O-​alkyl, OCH3, Cl, F, Br, iodo, NO2, NH2, NHCH3, NH-​alkyl, NHCOCH3, NHCO-​alkyl, NHSO2CH3, NHSO2-​alkyl, SO2CH3, SO2-​alkyl, SO2NH2, SO2NHCH2, SO2NH-​alkyl, SO2NHCOCH3, SO2NHCO-​alkyl, CO2H, CONHCH3, CONH-​alkyl, CO2CH3, CO2-​alkyl, CONHSO2CH3, CONHSO2-​alkyl, alkyl being as defined above for R1 and R2; wherein at least one of the substituents on the A ring is H;]​. [Provided that the compd. of general formula I is not: (E)​-​3-​phenyl-​1-​(2,​4,​6-​trimethoxy-​3-​(3-​methylbut-​2-​enyl)​phenyl)​prop-​2-​en-​1-​one or (E)​-​3-​phenyl-​1-​(2-​hydroxy-​4,​6-​dimethoxy-​3-​(3-​methylbut-​2-​enyl)​phenyl)​prop-​2-​en-​1-​one;] and tautomers, pharmaceutically acceptable salts and pro-​drugs thereof, of xanthohumol (II) and the use thereof. Thus, (E)​-​1-​[2,​4-​dihydroxy-​6-​methoxy-​3-​(3-​methylbut-​2-​enyl)​prenyl]​-​3-​(4-​fluorophenyl)​prop-​2-​en-​1-​one (III) was prepd. from 2',​4',​6'-​trihydroxyacetophenone monohydrate (IV·H2O) via regioselective O-​protection with MOM-​Cl in CH2Cl2 contg. DIPEA; O-​etherification with 3-​methyl-​2-​buten-​1-​ol in THF contg. PPh3 and DEAD;. Claisen rearrangement of the prenyl ether in N,​N-​dimethylaniline; O-​methylation with Me2SO4 in acetone contg. K2CO3; aldol condensation with 4-​FC6H4CHO in MeOH contg. aq. NaOH; and, demethoxymethylation with HCl in MeOH. The antitumor activity of III was detd. [significant inhibition of HUVEC cell growth at concn. of 20 μM after only 24 h; at the concn. of 10 μM it was proved able to reduce cell proliferation after 72 and 96 h treatment]​.