Benzothiazole compounds and their therapeutic use
First Claim
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1. A compound of the formula wherein R1 is C3-6 cycloalkyl, or C1-3 alkyl optionally substituted with one or more fluorine atoms;
- R2 is C1-6 alkyl, C3-6 cycloalkyl, CF3, CH2CF3, C2F5 or NR4R5;
R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) NR4R5 is a nitrogen-containing heterocyclic ring;
R6 is C1-3 alkyl; and
R7 and R8, which are the same or different, are each H, C1-3 alkyl, halogen, CF3 or CN, provided that both are not H;
or a pharmaceutically-acceptable salt thereof.
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Abstract
Compounds that are inhibitors of phosphodiesterase and have therapeutic utility, are of formula (i)
wherein R1 is C3-6 cycoalkyl, or C1-3 alkyl optionally substituted with one or more fluorine atoms;
R2 is C1-6 alkyl, C3-6 cycloalkyl, CF3, CH2CF3, C2F5 or NR4R5;
R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C)
NR4R5 is a nitrogen-containing heterocyclic ring;
R6 is C1-3 alkyl; and
R7 and R8, which are the same or different, are each H, C1-3 alkyl, halogen, CF3 or CN, provided that both are not H;
or a pharmaceutically-acceptable salt thereof
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Citations
17 Claims
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1. A compound of the formula
wherein R1 is C3-6 cycloalkyl, or C1-3 alkyl optionally substituted with one or more fluorine atoms; -
R2 is C1-6 alkyl, C3-6 cycloalkyl, CF3, CH2CF3, C2F5 or NR4R5;
R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) NR4R5 is a nitrogen-containing heterocyclic ring; R6 is C1-3 alkyl; and
R7 and R8, which are the same or different, are each H, C1-3 alkyl, halogen, CF3 or CN, provided that both are not H;
or a pharmaceutically-acceptable salt thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
2-ethyl-4-methoxybenzothiazole-7-carboxylic acid (3,5-dimethylisoxazol-4-yl) amide, 4-methoxy-2-(morpholin-4-yl)-benzothiazole-7-carboxylic acid (3,5-dimethylisoxazol-4-yl)amide, 2-cyclopropyl-4-methoxybenzothiazole-7-caboxylic acid (3,5-dimethylisoxazol-4-yl)amide, 4-methoxy-2-(piperidin-1-yl)-benzothiazole-7-carboxylic acid (3,5-dimethylisoxazol-4-yl)amide, 2-ethyl-4-methoxybenzothiazole-7-carboxylic acid (2-methyl-2H-pyrazol-3-yl)amide, 2-(4-tert-butoxycarbonylpiperazin-1-yl)-4-methoxybenzothiazole-7-caboxylic acid (3,5-dimethylisoxazol-4-yl)amide, 2-ethyl-4-methoxybenzothiazole-7-caboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide 4-methoxy-2-(morpholin-4-yl)-benzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)-amide, 4-methoxy-2-(piperidin-1-yl)benzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide, 2-(4-tert-butoxycarbonylpiperazin-1-yl)-4-methoxyenzothiazole-7-oxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide, 4-methoxy-2-(piperazin-1-yl)benzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide, trifluoroacetic acid salt, 4-methoxy-2-(piperazin-1-yl)benzothiazole-7-carboxylic acid (3,5-dimethylisoxazol-4-yl)amide, trifluoroacetic acid salt, and 4-methoxy-2-(4-methylpiperazin-1-yl)benzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide. -
10. The compound of claim 1, selected from the group consisting of
4-methoxy-2-trifluoromethylbenzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide and 2-cyclopropyl-4-methoxybenzothiazole-7-carboxylic acid (4-cyano-2-methyl-2H-pyrazol-3-yl)amide. -
11. A composition for use in therapy, comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
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12. A method for the treatment of a disease state that is capable of being modulated by inhibition of phosphodiesterase IV or Tumour Necrosis Factor, or that is a pathological condition associated with a function of phosphodiesterase IV, eosinophil accumulation or a function of the eosinophil, said method comprising administering to a person or animal an effective amount of the compound of claim 1.
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13. The method of claim 12, wherein the disease state is an inflammatory disease or autoimmune disease.
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14. The method of claim 12, wherein the disease state is selected from the group consisting of asthma, chronic bronchitis, chronic pulmonary inflammatory disease, chronic obstructive airways disease, atopic dermatitis, allergic rhinitis, psoriasis, arthritis, rheumatoid arthritis, joint inflammation, ulcerative colitis, Crohn'"'"'s disease, atopic eczema, stroke, bone resorption disease, multiple sclerosis and inflanmmatory bowel disease.
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15. The method of claim 12, wherein the disease state is selected from the group consisting of urticaria, allergic conjunctivitis, vernal conjunctivitis, inflammation of the eye, allergic responses in the eye, eosinophilic granuloma, gouty arthritis and other arthritic conditions, adult respiratory distress syndrome, diabetes insipidus, keratosis, cerebral senility, multi-infarct dementia, senile dementia, memory impairment associated with Parkinson'"'"'s disease, depression, cardiac arrest, intermittent claudication, rheumatoid spondylitis, osteoarthritis, sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, acute respiratory distress syndrome, cerebral malaria, silicosis, pulmonary sarcoidosis, reperfusion injury, graft vs host reaction, allograft rejection, infection-related fever or myalgia, malaria, HIV, AIDS, ARC, cachexia, keloid formation, scar tissue formation, pyresis, systemic lupus erythematosus, type 1 diabetes mellitus, Bechet'"'"'s disease, anaphylactoid purpura nephritis, chronic glomerulonephritis, leukaemla, tarditive dyskinesia, yeast or fungal infection, conditions requiring gastroprotection, and neurogenic inflammatory disease associated with irritation and pain.
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16. The method of claim 12, wherein the disease state is asthma.
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17. The method of claim 12, wherein the disease state is chronic obstructive airways disease or chronic bronchitis.
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Specification