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OwnerAmy Mae Bunker, Xue-Min Cheng +6inventors
InventorsAmy Mae Bunker, Xue-Min Cheng, Annette Marian Doherty, Jeremy John Edmunds, Gerald David Kanter, Chitase Lee, Joseph Thomas Repine, Richard William Skeean
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The instant invention is a series of benzothiazine dioxides, or a pharmaceutically acceptable salt thereof, which are potent endothelin A antagonists with profound in vitro activity, and improved syntheses for the Formula 1 1 The compounds are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure, and subarachnoid hemorrhage.
A method of treating subarachnoid hemorrhage comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating essential, renovascular, malignant, or pulmonary hypertension comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating congestive heart failure comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating cerebral ischemia or cerebral infarction comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating acute or chronic renal failure comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating cerebral vasospasm comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating cirrhosis comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating septic shock comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating endotoxic shock comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating arrhythmias comprising- administering to a host suffering therefrom a therapeutically effective amount of
A method of treating asthma comprising administering to a host suffering therefrom a therapeutically effective amount of
A-method of treating preeclampsia comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating atherosclerotic disorders comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating angina comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating cancer comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating benign prostatic hyperplasia comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating ischemic disease comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating gastric mucosal damage comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating hemorrhagic shock comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating ischemic bowel damage comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of treating diabetes comprising administering to a host suffering therefrom a therapeutically effective amount of
A method of inhibiting elevated levels of endothelin, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating subarachnoid hemorrhage, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating congestive heart failure, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating cerebral ischemia or cerebral infarction, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating acute or chronic renal failure, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating cerebral vasospasm, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating cirrhosis, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating septic shock comprising, administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating endotoxic shock, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating arrhythmias, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating asthma, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating preeclampsia, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating atherosclerotic disorders, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating angina, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating cancer, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating benign prostatic hyperplasia, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating ischemic disease, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating gastric mucosal damage, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating hemorrhagic shock, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating ischemic bowel damage, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
A method of treating diabetes, comprising administering to a host suffering therefrom a therapeutically effective amount of a compound which is 4-(7-ethyl-benzo[1,3]dioxol-5-yl)-1,1-dioxo-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.