Patent EP-1897864-A1 (EP)
Inventor: GERLACH MATTHIAS
IPC: A61K31/381
Filed: 2006-08-07
Abstract: Anthracene derivatives (I), are new, where (I) excludes e.g. 10-((E)-1-benzoyl-3-phenyl-allylidene)-10H-anthracen-9-one with chemical abstract service (CAS) registry no. of 262378-52-9, 10-(1-benzoyl-3-phenyl-prop-2-ynylidene)-10H-anthracen-9-one with CAS registry no. of 121747-08-8 and 10-[1,2-bis-(4-methoxy-phenyl)-2-oxo-ethylidene]-10H-anthracen-9-one with CAS registry no. of 63370-49-0. Anthracene derivatives of formula (I), are new, where (I) excludes 10-((E)-1-benzoyl-3-phenyl-allylidene)-10H-anthracen-9-one with chemical abstract service (CAS) registry no. of 262378-52-9, 10-(1-benzoyl-3-phenyl-prop-2-ynylidene)-10H-anthracen-9-one with CAS registry no. of 121747-08-8, 10-[1,2-bis-(4-methoxy-phenyl)-2-oxo-ethylidene]-10H-anthracen-9-one with CAS registry no. of 63370-49-0, 10-(2-oxo-1,2-diphenyl-ethylidene)-10H-anthracen-9-one with CAS registry no. of 19661-62-2, 10-(2-Oxo-2-phenyl-ethylidene)-10H-anthracen-9-one with CAS registry no. of 17665-75-7, 2-(4,5-dihydroxy-10-oxo-10H-anthracen-9-ylidene)-succinic acid dimethyl ester with CAS registry no. of 83498-19-5, 10-(2-oxo-1-phenyl-propylidene)-10H-anthracen-9-one with CAS registry no. of 42866-43-3, 10-(1-methyl-2-oxo-propylidene)-10H-anthracen-9-one with CAS registry no. of 3095926 and 10-(2-oxo-1-phenyl-butylidene)-10H-anthracen-9-one with CAS registry no. of 42866-49-9. X : O, S, NR 1>1>, N-OR 1>2>, geminal bonded hydrogen or OH; Y 1>O, S, NR 1>3>or N-OR 1>4>; R 1>-R 8>H, optionally substituted (cyclo)alkyl, optionally substituted cyclodialkyl, optionally substituted heterocycle, optionally substituted heterocycle-alkyl, optionally substituted aryl, optionally substituted aryl-alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-alkyl, amino, mono-alkylamino, di-alkylamino, F, Cl, Br, I, alkyl with one or more substituted F atoms, trifluoromethyl, CN, cyano-alkyl, carbonyl, carboxyl, COOH, alkoxycarbonyl, carboxy-alkyl, alkoxycarbonyl-alkyl, OH, alkoxy, aryl-alkoxy, benzyloxy, heteroaryl-alkoxy, alkoxycarbonylamino or alkoxycarbonylamino-alkyl; R 9>optionally substituted (cyclo)alkyl, optionally substituted cyclodialkyl, optionally substituted heterocycle, optionally substituted heterocycle-alkyl, optionally substituted (hetero)aryl, optionally substituted aryl-alkyl, optionally substituted heteroaryl-alkyl, -OR 1>5>or -1NR 1>6>R 1>7>; R 1>0>H, optionally substituted alkyl, optionally substituted (hetero)aryl, optionally substituted aryl-alkyl or optionally substituted heteroaryl-alkyl; and R 1>1>-R 1>7>H, optionally substituted (cyclo)alkyl, optionally substituted cyclodialkyl, optionally substituted heterocycle, optionally substituted heterocycle-alkyl, optionally substituted (hetero)aryl, optionally substituted aryl-alkyl or optionally substituted heteroaryl-alkyl. Independent claims are included for: (1) the preparation of (I); (2) a pharmaceutical composition comprising (I); and (3) a medicament comprising (I). [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : Tubulin polymerization inhibitor; Microtubuli-based motor protein inhibitor. The tubilin polymerization inhibitory activity of (I) was tested in-vitro. The results showed that the EC 50value of 10-[2-(3,4-dihydroxy-phenyl)-2-oxo-ethylidene]-10H-anthracen-9-one was 7.15/8.02 mu g/ml.