The present invention provides active metablites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

The present invention provides active metablites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.

The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.

The present inventions relates to a method for the production of gellan gum, under mixing conditions, the method comprising a) providing a fermentation broth or other liquid medium containing gellan gum, b) if necessary adjusting the temperature and the pH of the fermentation broth/liquid medium to allow or facilitate enzymatic treatment in step c, c) adding one or more enzymes capable of reducing or abolishing the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase, said one or more enzymes being added in an amount sufficient to reduce or abolish the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase in the broth/liquid medium, and/or treating the broth/liquid medium at a temperature between 90° C. and 125° C. for a period of time sufficient to reduce or abolish the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase in the broth/liquid medium, and d) optionally recovering the gellan gum from the gellan gum containing broth/liquid medium.

The present inventions relates to a method for the production of gellan gum, under mixing conditions, the method comprising a) providing a fermentation broth or other liquid medium containing gellan gum, b) if necessary adjusting the temperature and the pH of the fermentation broth/liquid medium to allow or facilitate enzymatic treatment in step c, c) adding one or more enzymes capable of reducing or abolishing the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase, said one or more enzymes being added in an amount sufficient to reduce or abolish the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase in the broth/liquid medium, and/or treating the broth/liquid medium at a temperature between 90° C. and 125° C. for a period of time sufficient to reduce or abolish the enzymatic activity of S. elodea derived arylsulfatase and/or β-glucuronidase in the broth/liquid medium, and d) optionally recovering the gellan gum from the gellan gum containing broth/liquid medium.

Methods are provided for modulating the activity of multimeric ubiquitin-protein E3 ligases including, but not limited to, E6AP ligase activities. The methods reduce the level of oligomer formation such as homotrimeric E6AP ligase to reduce the enzyme activity. Alternatively, agents are provided that can promote the association of the ligase monomers, thereby increasing the ligase activity. Accordingly, novel therapeutic strategies are provided that are useful for the treatment of pathologies resulting from mutations in the genes encoding the ligases and which adversely increase or decrease a ubiquitination reaction.

Methods are provided for modulating the activity of multimeric ubiquitin-protein E3 ligases including, but not limited to, E6AP ligase activities. The methods reduce the level of oligomer formation such as homotrimeric E6AP ligase to reduce the enzyme activity. Alternatively, agents are provided that can promote the association of the ligase monomers, thereby increasing the ligase activity. Accordingly, novel therapeutic strategies are provided that are useful for the treatment of pathologies resulting from mutations in the genes encoding the ligases and which adversely increase or decrease a ubiquitination reaction.

The invention provides compounds of formula (I) with substituents as specified in claim 1 for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceuticals compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to over-expression of O-GlcNAcase or accumulation of O-GlcNac. ##STR00001##

The invention provides compounds of formula (I) with substituents as specified in claim 1 for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceuticals compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to over-expression of O-GlcNAcase or accumulation of O-GlcNac. ##STR00001##