Patent DE-102007063056-A1 (DE)
Title: New anthraquinone derivatives are protein kinase inhibitors useful e.g. to treat autoimmune-, inflammatory-, metabolic-, organ-, cardiovascular-, neurological and neurodegenerative-, hormone dependent-disease, asthma, depression and stroke
Inventor: GEBHARDT ROLF
IPC: A61P3/10
Filed: 2007-12-28
Abstract: Anthraquinone derivatives (I) and their tautomers are new, where (I) excludes e.g. 4-(2-hydroxyethyl)-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(2-aminoethyl))-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(N-morpholino))-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(3-aminopropyl))-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, and 4-cyclohexylamino-1,3,8-trihydroxy-6-methylarithracen-9,10-dione. Anthraquinone derivatives of formula (I) and their tautomers are new, where (I) excludes 4-(2-hydroxyethyl)-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(2-aminoethyl))-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(N-morpholino))-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N-(3-aminopropyl))-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-cyclohexylamino-1,3,8-trihydroxy-6-methylarithracen-9,10-dione, 4-(N-piperindino)-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N'N'-2-dimethylaminoethyl)-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(3'-(N'-benzoyl)-aminopropyl)-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(3'-(N'-(2''-carboxy)-benzoylaminopropyl))-amino-1,3,8-trihydroxy-6-methylanthracen-9,10-dione, 4-(N'-3-acetylaminopropyl)-amino-1,3,8-trihydroxy-6-methylanthracen-9, 10-dione, 4,6-dihydroxy-2-methyl-8a,9,10,11-tetrahydro-8-oxa-11a-aza-pentaleno-[1,2-a]anthracen-5,12-dione and 7,9-dihydroxy-11-methyl-1,2,3,4,4a,5,14,14a-octahydro-naphtho-[2,3-a]phenazin-8,13-dione. R 1>-R 3>H, (cyclo)alkyl, aryl, acyl and/or glycosyl; R 4>alkyl, (hetero)aryl, heteroaryl, amino methyl, amino ethyl, hydroxymethyl, carbonyl, carboxyl, carboxyamidyl, monohalomethyl, dihalomethyl, trihalomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, cyclic N-alkylaminomethyl, trialkylammoniummethyl; R 5>, R 6>H, alkyl, acyl, cycloalkyl, heterocycloalkyl, hydroxyalkyl, haloalkyl, ureido, guanidino, thioureido and/or aminoalkyl; and R 7>-R 9>H, alkyl, aryl, heteroalkyl, heteroaryl, amino methyl, hydroxymethyl, carbonyl, carboxyl, carboxyamidyl, monohalomethyl, dihalomethyl and/or trihalomethyl. Independent claims are included for: (1) the preparation of (I); and (2) a pharmaceutical composition comprising (I) and their salts, one or more auxiliary agents, carrier materials or diluents. [Image] ACTIVITY : Immunosuppressive; Antiinflammatory; Metabolic; Cardiovascular-Gen.; Neuroprotective; Antiasthmatic; Nootropic; Antiparkinsonian; Anticonvulsant; Neuroleptic; Antidepressant; Cerebroprotective; Vasotropic; Cardiant; Cytostatic; Antidiabetic; Hepatotropic; Endocrine-Gen.; Antimanic. MECHANISM OF ACTION : Protein kinase inhibitor; Beta-catenin signaling pathway inhibitor. The ability of (I) to inhibit casein kinase I was tested using cell-free protein kinase assay. The results showed that 4-[N-(3-aminopropyl)-amino]-1,3,8-trihydroxyanthracen-9,10-dione exhibited an IC 5 0value of 1.8 mu M.