Methods for treating PDEIV-mediated diseases or conditions

Abstract

The present invention provides methods and compositions for the treatment of PDEIV-mediated diseases or conditions, including inflammatory diseases or conditions. [Solution] Use the compound of formula (I) or a pharmaceutically acceptable salt thereof. JPEG2026102632000030.jpg27128

Claims

1. A pharmaceutical agent for treating a phosphodiesterase IV (PDEIV)-mediated disease or condition in a patient requiring treatment for such a disease or condition, comprising a compound of formula (I): 【Chemistry 1】 or containing a pharmaceutically acceptable salt thereof, The PDEIV-mediated disease or condition is an immunodeficiency, lupus, vitiligo, COPD, asthma, Behçet's syndrome, uveitis, allergic conjunctivitis, cytokine-mediated disease, neutrophil-mediated disease, or neurodegenerative disorder, as described in the medical text.

2. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is an immune disorder.

3. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is vitiligo.

4. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is asthma.

5. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is COPD.

6. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is allergic conjunctivitis.

7. The pharmaceutical product according to claim 6, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof in an amount effective for reducing the signs or symptoms of allergic conjunctivitis.

8. The pharmaceutical product according to claim 7, wherein the signs or symptoms of allergic conjunctivitis are itchy eyes, redness of the conjunctiva, redness of the ciliary body, redness of the episclera, conjunctival edema, swelling of the eyelids, lacrimation, runny nose, itching of the nose, itching of the ear or palate, or nasal congestion.

9. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is a cytokine-mediated disease.

10. The PDEIV-mediated diseases or conditions include periodontitis, xerophthalmia, rheumatoid arthritis, osteoarthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis, traumatic arthritis, rubella arthritis, inflammatory bowel disease, multiple sclerosis, graft disease, systemic lupus erythematosus, toxic shock syndrome, irritable bowel syndrome, muscle degeneration, allograft rejection, pancreatitis, insular pancreatitis, glomerulonephritis, diabetic nephropathy, renal fibrosis, chronic kidney disease, gout, leprosy, acute synovitis, Reiter's syndrome, gouty arthritis, Behçet's disease, spondylitis, endometriosis, intervertebral disc syndrome, bursitis, tendinitis, tenosynovitis, or This includes, but is not limited to, non-articular inflammatory conditions such as fibromyalgia syndrome, acute or chronic pain, neuralgia, neuropathy, polyneuropathy, diabetes-related polyneuropathy, trauma, migraine, tension and cluster headaches, Horton's disease, varicose vein ulcers, neuralgia, skeletal muscle pain, bone trauma pain, fractures, painful osteodystrophy, spondyloarthritis, fibromyalgia, phantom limb pain, back pain, spinal pain, postoperative pain, herniated disc-induced sciatica, cancer-related pain, vascular pain, visceral pain, childbirth, HIV-related pain, allergies, metabolic diseases, chemotherapy / radiation-related complications, type 1 diabetes, type 2 diabetes. Type, liver disease, gastrointestinal disorders, eye diseases, allergic conjunctivitis, diabetic retinopathy, Sjögren's syndrome, uveitis, lung disease, kidney disease, HIV-related cachexia, cerebral malaria, ankylosing spondylitis, leprosy, anemia, fibromyalgia, renal failure, stroke, chronic heart failure, endotoxemia, reperfusion injury, ischemia-reperfusion, myocardial ischemia, restenosis, thrombosis, angiogenesis, coronary artery disease, coronary artery disease, acute coronary syndrome, Takayasu's arteritis, heart failure including cardiac dysfunction, aortic stenosis, cardiomyopathy, myocarditis, vasculitis, vascular restenosis, valvular heart disease, coronary artery bypass, hypercholesterolemia, acute venous thrombosis, lung Diseases or conditions related to blood coagulation or fibrinolysis, such as arterial embolism, thrombosis during pregnancy, hemorrhagic skin necrosis, acute or chronic disseminated intravascular coagulation (DIC), thrombus formation from surgery, prolonged bed rest or immobility, venous thrombosis, fulminant meningococcal bacteremia, acute thrombotic stroke, acute coronary vein occlusion, acute peripheral arterial occlusion, massive pulmonary embolism, axillary vein thrombosis, massive iliofemoral vein thrombosis, occlusive arterial or venous cannula, cardiomyopathy, hepatic vein embolism, hypotension, decreased cardiac output, decreased vascular resistance, pulmonary hypertension, decreased lung compliance, leukopenia or thrombocytopenia;Atherosclerosis, uveitis, glaucoma, optic neuritis, retinal ischemia, diabetic retinopathy, laser-induced optic nerve injury, or surgery or trauma-induced proliferative vitreoretinopathy, allergic rhinitis, asthma, adult respiratory distress syndrome, chronic pneumonia, chronic obstructive pulmonary disease, emphysema, bronchitis, mucus overgrowth, silicosis, SARS infection and airway inflammation, eczema, Guillain-Barré syndrome, Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and other demyelinating diseases, viral and bacterial meningitis, CNS trauma, spinal cord injury, seizures, convulsions, olivopontocerebellar atrophy, AIDS dementia complications, MERRF and MELAS syndromes, Leber disease, Wernicke encephalopathy, Rett syndrome, homocystinuria, hyperprolinemia, hyperhomocysteinemia, nonketotic hyper The pharmaceutically acceptable drug according to claim 1, which is glycinemia, hydroxybutyrate amino aciduria, sulfite oxidase deficiency, complex disorders, lead encephalopathy, Tourette syndrome, hepatic encephalopathy, drug addiction, drug tolerance, drug dependence, depression, anxiety and schizophrenia, aneurysm, epilepsy, resorbable bone disease, osteopetrosis, osteoporosis or osteoarthritis, diabetes mellitus, systemic cachexia, cachexia secondary to infection or malignant tumor, cachexia secondary to acquired immunodeficiency syndrome (AIDS), obesity, anorexia or neurotoxic vesicular disease, sepsis, HIV, HCV, malaria, infectious arthritis, leishmaniasis, Lyme disease, cancer including but not limited to breast cancer, colon cancer, lung cancer, and prostate cancer, multiple myeloma, acute myeloid leukemia, myelodysplastic syndrome, non-Hodgkin lymphoma, follicular lymphoma, Castleman disease, or drug resistance.

11. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is a neutrophil-mediated disease.

12. The pharmacopoeia according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is bronchial asthma, rhinitis, influenza, stroke, myocardial infarction, burns, adult respiratory distress syndrome (ARDS), post-traumatic multi-organ injury, acute glomerulonephritis, skin disease with acute inflammatory components, acute purulent meningitis, hemodialysis, leukocyte apheresis, granular transfusion-associated syndrome, or necrotizing enterocolitis.

13. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is a neurodegenerative disorder.

14. The pharmacopoeia according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is inflammatory colitis selected from the group consisting of Alzheimer's disease; Parkinson's disease; Crohn's disease and ulcerative colitis; diarrhea; liver disease selected from the group consisting of autoimmune hepatitis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis and fulminant hepatic failure; gastrointestinal disease selected from the group consisting of celiac disease and nonspecific colitis; osteoporosis; lung disorder selected from the group consisting of allergic rhinitis, asthma, chronic obstructive pulmonary disease, chronic granulomatous inflammation, cystic fibrosis and sarcoidosis; cardiovascular disease selected from the group consisting of atherosclerotic heart disease, congestive heart failure and restenosis; or kidney disease selected from the group consisting of glomerulonephritis and vasculitis.

15. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is uveitis.

16. The pharmaceutical product according to claim 1, wherein the phosphodiesterase IV (PDEIV)-mediated disease or condition is Behçet's syndrome.

17. The pharmaceutical product according to claim 1, wherein the patient is a human being.

18. The pharmaceutical product according to claim 1, wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered as a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

19. The pharmaceutical product according to claim 1, wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered topically, orally, orally, as a suppository, intravenously, parenterally, intraperitoneally, intramuscularly, intralesionally, intraarachnoidally, intranasally, or subcutaneously.

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