PYRIDAZINONE ALDOSE REDUCTASE INHIBITORS.

摘要

THE PRESENT INVENTION RELATES TO NOVEL PYRIDAZINONE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS COMPRISING THOSE COMPOUNDS AND TO METHODS OF USING SUCH COMPOUNDS AND COMPOSITIONS TO INHIBIT ALDOSE REDUCTASE, LOWER SORBITOL LEVELS AND, THUS, LOWER FRUCTOSE LEVELS, AND/OR TREAT OR PREVENT DIABETIC COMPLICATIONS SUCH AS DIABETIC NEUROPATHY, DIABETIC RETINOPATHY, DIABETIC NEPHROPATHY, DIABETIC CARDIOMYOPATHY, DIABETIC MICROANGIOPATHY AND DIABETIC MACROANGIOPATHY IN MAMMALS. THIS INVENTION ALSO RELATES TO METHODS OF AFFORDING CARDIOPROTECTION TO SUBJECTS NOT SUFFERING FROM DIABETES. THIS INVENTION ALSO RELATES TO PHARMACEUTICAL COMPOSITIONS AND KITS COMPRISING A COMBINATION OF AN ALDOSE REDUCTASE INHIBITOR (ARI) OF THIS INVENTION AND A SORBITOL DEHYDROGENASE INHIBITOR AND TO METHODS OF USING SUCH COMPOSITIONS OR KITS TO TREAT OR PREVENT THE ABOVE DIABETIC COMPLICATIONS IN MAMMALS. THIS INVENTION ALSO RELATES TO OTHER COMBINATIONS WITH THE ARIS OF THIS INVENTION, INCLUDING COMBINATIONS WITH ADENOSINE AGONISTS; NHE-1 INHIBITORS; GLYCOGEN PHOSPHORYLASE INHIBITORS; SELECTIVE SEROTONIN REUPTAKE INHIBITORS; GABA AGONISTS; ANTIHYPERTENSIVE AGENTS; 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE INHIBITORS; PHOSPHODIESTERASE-5 INHIBITORS; AND TO GLUCOSE LOWERING AGENTS.