57 results about "Protein kinase modulator" patented technology

Substituted aryl 1,4-pyrazine derivatives and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

The invention provides compounds that inhibit CK2 and / or Pim kinases and compositions containing such compounds. These tricyclic compounds and compositions containing them are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, pathogenic infections, and certain immunological disorders.

This invention relates to compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion, and to pharmaceutical compositions containing such compounds. Even more specifically, the invention relates to compounds that inhibit, regulate and / or modulate kinases, particularly Checkpoint Kinases, even more particularly Checkpoint Kinase 1, or Chk1. Methods of therapeutically or prophylactically using the compounds and compositions to treat kinase-dependent diseases and conditions are also an aspect of the invention, and include methods of treating cancer, as well as other disease states associated with unwanted angiogenesis and / or cellular proliferation, by administering effective amounts of such compounds.

The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and / or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

The present invention provides, inter alia, compounds of formula I as protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and / or amelioration of kinase mediated diseases or disorders with them.

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and / or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

The present invention relates to chemical compounds having a general formula Iwherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

The present disclosure relates to tirazalopyridazine protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.

The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and / or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

The present disclosure provides heterocyclic protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.

The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and / or amelioration of kinase mediated diseases or disorders with them.

The present invention provides pyrazolothiazole kinase modulators, methods of treating certain disease states, such as cancer, and pharmaceutical composition thereof.

Methods for reducing injury to a transplanted mammalian organ or tissue, including inhibiting the development of graft blood vessel disease, are provided. In one form, a method includes administering compositions that include one or more PKC regulators to an organ or tissue donor and an organ or tissue recipient. Methods for decreasing or otherwise modulating an inflammatory response in a mammal are also provided. In one form, a method includes administering one or more regulators of protein kinase C to a patient in need thereof prior to, during or after an event giving rise to an inflammatory response. Methods for inhibiting, or otherwise modulating, a pro-apoptotic event are also provided. In one form, a method includes administering a therapeutically effective amount of an agonist of ε protein kinase C, and optionally an inhibitor of δ protein kinase C.

The present disclosure provides heterocyclic protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.

The present invention provides, inter alia, compounds of formula I as protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and / or amelioration of kinase mediated diseases or disorders with them.

The present disclosure relates to triazolopyridazine protein kinase modulators of Formula (I), methods of using these compounds to treat diseases mediated by kinase activity.

The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and / or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.

The present invention provides new tyrphostin derivatives acting as protein tyrosine kinase (PTK) inhibitors and receptor tyrosine kinase (RTK) inhibitors, and / or which directly or indirectly affect proteins in the PTK-mediated signal transduction pathway, methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for preventions and treatments of PTK and RTK related disorders such as metabolic, fibrotic, and cell proliferative disorders, in particular psoriasis and cancer.

The present invention provides new tyrphostin derivatives acting as substrate competitive protein tyrosine kinase (PTK) inhibitors and receptor tyrosine kinase (RTK) inhibitors, methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for preventions and treatments of PTK and RTK related disorders such as metabolic, fibrotic, and cell proliferative disorders, in particular psoriasis and cancer.

The invention provides compounds that inhibit CK2 and / or Pim kinases and compositions containing such compounds. These tricyclic compounds and compositions containing them are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, pathogenic infections, and certain immunological disorders.

The present invention provides compounds useful as c-Met protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and / or amelioration of c-Met kinase mediated disease or disorders with them.

The present invention provides deuterated compounds having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. The deuterated compounds of the invention can modulate casein kinase (CK) activity and / or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such deuterated compounds as therapeutic agents.

The invention provides a composition comprising (S) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol, wherein the composition is either substantially free of (R) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol or the composition contains a mixture of the (S) and (R) enantiomers in which the (S) enantiomer predominates. Also provided are processes for the preparation of the (S) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanok novel process intermediates and methods for making the novel process intermediates.

The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between Rand NR<2>R<3> and a maximum chain length of 4 atoms extending between E and NR<2>R<3>, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the inker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR<2>R<3> group and provided that the oxo group when present is located at a carbon atom a with respect to the NR<2>R<3> group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R is an aryl or heteroaryl group; and R<2>, R<3>, R<4> and R<5> are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

The present invention relates to dual delta (δ) and gamma (γ) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and / or amelioration of Pi3K kinase mediated diseases or disorders with them.