144 results about "Rho kinase inhibitor" patented technology

Disclosed are compounds and derivatives thereof, their synthesis, and their use as Rho-kinase inhibitors. These compounds are useful for inhibiting tumor growth, treating erectile dysfunction, and treating other indications mediated by Rho-kinase, e.g., coronary heart disease.

Methods for using 6-aminoimidazo[1,2-b]pyridazine analogs are disclosed herein to treat rho kinase-mediated diseases or rho kinase-mediated conditions, including controlling intraocular pressure and treating glaucoma, are disclosed. Ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma, and additionally useful for controlling intraocular pressure, the compositions comprising an effective amount of 6-aminoimidazo[1,2-b]pyridazine analogs, are disclosed herein.

The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

The present invention relates to an aqueous pharmaceutical formulation comprising at least one inhibitor of Rho-associated protein kinase (ROCK). The aqueous pharmaceutical formulation comprises 0.01-0.4% w / v of ROCK inhibitor(s), a non-ionic surfactant in an amount of 0.01-2% w / v, and a tonicity agent to maintain a tonicity between 220-360 mOsm / kG, at a pH between 6.3 to 7.8, wherein the ROCK inhibitor, the surfactant, and the tonicity agent are compatible in the formulation. The aqueous ophthalmic formulations of this invention have an increased ocular bioavailability and / or aqueous humor concentrations without a concomitant increase in systemic concentrations. The present invention further provides a method of reducing intraocular pressure, particularly a method of treating glaucoma, by administering the aqueous pharmaceutical formulation to a subject.

This invention is directed to methods of preventing or treating ocular diseases with inflammation, excessive cell proliferation, remodeling, neurite retraction, corneal neurodegeneration, excessive vaso-permeability and edema. Particularly, this invention relates to methods treating ocular diseases such as allergic conjunctivitis, corneal hyposensitivity, neurotrophic keratopathy, dry eye disease, proliferative vitreal retinopathy, macular edema, macular degeneration, and blepharitis, using novel Rho kinase inhibitor compounds. The method comprises identifying a subject in need of the treatment, and administering to the subject an effective amount of a novel Rho kinase inhibitor compound to treat the disease.

This invention is directed to methods of preventing or treating neurological or neuropathic diseases or conditions associated with excessive inflammation, neurodegeneration, neuro-remodeling, and axonal / neurite retraction. Particularly, this invention relates to methods treating neurological or neuropathic diseases such as cerebral ischemia, stroke, neuropathic pain, spinal cord injury, Alzheimer's disease, and multiple sclerosis, using novel rho kinase inhibitor compounds. The method comprises identifying a subject in need of the treatment, and administering to the subject an effective amount of a novel rho kinase inhibitor compound to treat the disease.

Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.

The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

The present invention provides compounds of formula I:These compounds, and pharmaceutically acceptable compositions thereof, are useful generally as kinase inhibitors, particularly as inhibitors of PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, and Aurora-2. Accordingly, compounds and compositions of the invention are useful for treating or lessening the severity of a variety of disorders, including, but not limited to, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative disorders, infectious diseases and viral diseases.

This invention is directed to methods of preventing or treating diseases or conditions associated with alterations in cellular integrity including alterations in endothelial permeability, excessive cell proliferation or tissue remodeling. Particularly, this invention is directed to methods of treating diabetic nephropathy, malaria, or cancer. The method comprises identifying a subject in need of the treatment, and administering to the subject an effective amount of a novel rho kinase inhibitor compound to treat the disease.

The present invention is directed to a method for preventing or decreasing the incidence of or treating aneurysm or cardiac hypertrophy, comprising administering an effective amount of a rho-kinase inhibitor, such as fasudil, to a subject in need thereof.

The present invention relates to inhibitors of ROCK1 and ROCK2, which may be selective for ROCK2, and methods of modulating the pharmacokinetic and / or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and / or ROCK2. Also provided are treatments combining inhibitors of ROCK1 and / or ROCK2 with statins.

The present invention provides methods for making, delivering and using formulations that combine a therapeutically active agent(s) (such as for example a Rho antagonist(s)) and a flowable carrier component capable of forming a therapeutically acceptable matrix in vivo (such as for example tissue adhesives), to injured nerves to promote repair and regeneration and regrowth of injured (mammalian) neuronal cells, e.g. for facilitating axon growth at a desired lesion site. Preferred active agents are known Rho antagonists such as for example C3, chimeric C3 proteins, etc. or substances selected from among known trans-4-amino(alkyl)-1-pyridylcarbamoylcyclohexane compounds or Rho kinase inhibitors. The system for example may deliver an antagonist(s) in a tissue adhesive such as, for example, a fibrin glue or a collagen gel to create a delivery matrix in situ. A kit and methods of stimulating neuronal regeneration are also included.

The present invention provides compositions and methods of use thereof to prevent and / or treat pathogenic infection. In particular, the present invention provides the use of kinase inhibitors to inhibit kinases that involve in pathogen-host cell interactions that are associated with or cause pathogenic infections, therefore, to effectively prevent and / or treat pathogenic infections with far less likely to engender resistance as compared to conventional antibiotics and anti-viral drugs. The present invention further provides the use of kinase inhibitors for the treatment of acute pathogenic infections for a short period of time to avoid toxicities that may caused by long term use of these kinase inhibitors.

The present invention relates to novel Anilinopiperazine Derivatives of formula (I), compositions comprising the Anilinopiperazine Derivatives, and methods for using the Anilinopiperazine Derivatives for treating or preventing a proliferative disorder, an anti-proliferative disorder, inflammation, arthritis, a central nervous system disorder, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral disease, a fungal infection, or a disorder related to the activity of a protein kinase.

There is provided a preventive for glaucoma or a preventive or a remedy for ocular hypertension, with a potent ocular hypotensive effect and prolonged duration thereof. A preventive or a remedy for glaucoma comprising a Rho kinase inhibitor and an α1 blocker in combination.

Disclosed are compounds and derivatives thereof their synthesis, and their use as Rho-kinase inhibitors. These compounds of the present invention are useful for inhibiting tumor growth, treating erectile dysfunction, and treating other indications mediated by Rho-kinase, e.g., coronary heart disease.