Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.

Histone deacetylase inhibitors

The present invention provides a compound of formula I: or a pharmaceutically acceptable salt or mixtures thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK mammalian protein kinase, and more particularly inhibitors of GSK-3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.

Compositions useful as inhibitors of protein kinases

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Heterocyclic compounds and uses thereof

The invention relates to compounds of formula (I) in which formula X is hydrogen or hydroxy; R?1 and R2? stand for hydrogen or a C?1?-C6 hydrocarbyl radical; or taken together with the carbon atom bearing the group X, can form a C3-C8 carbocyclic ring; R?3? stands for hydrogen or a C?1?-C10 hydrocarbyl radical or for YR?4?, in which Y stands for the radicals -CO-, -CO-O-, -CO-S-, -CS-, -CS-O-, -CS-S-, -SO- or -SO?2?-, and R?4? stands for hydrogen or a C?1?-C10 hydrocarbyl radical; Q is a single bond or a C1-C8 hydrocarbylene diradical. R?1, R2, R3? and/or Q may be optionally substitued with one or more deuterium or fluorine atoms. The compounds show an antiinflammatory and immunomodulating effect as well as strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells.

Novel vitamin d analogues

The present invention relates to immunosuppressant, process for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG receptor mediated signal transduction.

Immunosuppressant compounds and compositions

Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10-(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO2; R1 is aryl; R2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R2 cannot represent 2-phthalimidyl, and in case of Y = SO2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as vegf receptor tyrosine kinase inhibitors

New 20-methyl-substituted vitamin D derivates have general formula (I), in which R1 is a hydrogen atom, a hydroxyl group or an alkanoyloxyl group with 1 to 12 carbon atoms or a benzoyloxyl group, R2 is a hydrogen atom or an alkanoyl group with 1 to 12 carbon atoms or a benzoyl group; and R3 is saturated or unsaturated, straight-chain or branched-chain hydrocarbon residue with up to 18 C atoms, possibly interrupted and/or substituted by one or several carbocyclic structures (C?3-10?-cycloalkyl or cycloakenyl residues, the latter having up to 2 double bonds), possibly substituted by one or several hydroxyl, oxo, amino groups and/or by one or several halogen atoms, possibly having one or several oxygen, sulphur and/or nitrogen (as (a)) atoms as chaining members in the hydrocarbon residue. Also disclosed is a process for preparing the same. These new compounds have a strongly improved induction of cell differentiation (HL-60), with respect to calcitriol, and are suitable for preparing medicaments.

20-methyl-substituted vitamin d derivates

Substituted anthranilamides and use thereof as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis as well as their intermediate products for the production of anthranilamides are described.

Anthranyl amides and their use as medicaments

23-Oxa-derivatives in the vitamin D series of formula I ##STR1## are described in which R1, R2 and R4 independently of one another mean a hydrogen atom or an acyl group with 1 to 9 carbon atoms, R3 each means a hydrogen atom or each a linear or branched alkyl group with 1 to 4 carbon atoms and X means an alkylene radical--(CH2)n -- with n=1, 2, 3, and if n=1, R3 each cannot be a methyl or propyl group, as well as a process for their production. The compounds have proliferation-inhibiting and cell-differentiation effects and are suitable for the production of pharmaceutical agents.

23-oxa-derivatives in the vitamin D series, process for their production, pharmaceutical preparations containing these derivatives as well as their use pharmaceutical agents

The invention concerns novel vitamin D derivatives with C-25 substituents of general formula (I). The invention also concerns a process for their preparation and their use in preparing medicaments.

Haberey Martin

Papers

N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as vegf receptor tyrosine kinase inhibitors

20-methyl-substituted vitamin d derivates

Anthranyl amides and their use as medicaments

23-oxa-derivatives in the vitamin D series, process for their production, pharmaceutical preparations containing these derivatives as well as their use pharmaceutical agents

Novel vitamin d derivatives with c-25 substituents, process for their preparation, intermediate products and their use in preparing medicaments