Inspire Pharmaceuticals, Inc.

Other

Ward M Peterson

Benjamin R Yerxa

Christopher S Crean

John W Lampe

Edward G Brown

Janet L Rideout

William Pendergast

Sammy Ray Shaver

Paul Steven Watson

James G Douglass, Iii

Tomas Navratil

David J Slade

Jason L Vittitow

Jonathan Bryan DeCamp

Nicholas F Pelz

Emilee H Fulcher

José L Boyer

Robert Plourde, Jr

Scott D Sorensen

Matthew S Cowlen

Jesus Jeronimo Pintor

Maria A Peral

Zhen Zhang

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.

Cytoskeletal active rho kinase inhibitor compounds, composition and use

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.

Method for treating diseases associated with alterations in cellular integrity using Rho kinase inhibitor compounds

This invention is directed to methods of preventing or treating diseases or conditions of the lungs associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema. Particularly, this invention is directed to methods of treating pulmonary diseases such as asthma; chronic obstructive pulmonary disease; respiratory tract illness caused by respiratory syncytial virus; pulmonary arterial hypertension; acute respiratory distress syndrome and ventilator induced lung injury; cystic fibrosis; bronchiectasis; alpha-1-antitrypsin deficiency; rhinitis; rhinosinusitis; primary ciliary dyskinesia; pneumonia; bronchiolitis caused by agents other than respiratory syncytial virus; and interstitial lung disease including lymphangioleiomyomatosis; idiopathic pulmonary fibrosis; obliterative bronchiolitis or bronchiolitis obliterans organizing pneumonia due to lung transplantation or HSCT; nonspecific interstitial pneumonia; cryptogenic organizing pneumonia; acute interstitial pneumonia; respiratory bronchiolitis-associated interstitial lung disease; or pulmonary sarcoidosis. The method comprises administering to a subject an effective amount of a rho kinase inhibitor compound to treat the disease.

Method for treating pulmonary diseases using rho kinase inhibitor compounds

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.

Method for treating neurological and neuropathic diseases using rho kinase inhibitor compounds

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention also provides a method of treating sinusitis. The present invention further provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

P1-(2'-deoxycytidine 5&#x2032;-)P4-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, for treating sinusitis

The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Degradation-resistant mononucleoside phosphate compounds

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention further provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-) tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-) tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

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The present invention provides a method of preventing or treating an inflammatory disease, including but not limited to, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular diseases, glomerulonephritis, inflammatory skin diseases, and sarcoidosis. The method comprises administrating to a subject a pharmaceutical formulation comprising a nucleotide receptor agonist, such as nucleoside diphosphate, nucleoside triphosphate, or dinucleoside polyphosphate, according to general formula Ia, Ib, IIa, IIb, or III. Preferred indications of the present invention are perennial allergic rhinitis, seasonal allergic rhinitis, infectious allergic rhinitis, and allergic conjunctivitis.

Method for treating or preventing inflammatory diseases

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphate salts. The present invention also provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof

The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.

Compositions for treating epithelial and retinal tissue diseases

The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

Method for reducing intraocular pressure

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.

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Morrisville, NC, United States of America

Ward M Peterson