N1-pyrazolospiroketone acetyl-CoA carboxylase inhibitors
The invention provides a compound of Formula (1) or a pharmaceutically acceptable salt of the compound, wherein R 1 , R 2 , R 3 , Z, A 1 , L and A 2 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.
1. A method for treating a disease, condition or disorder mediated by the inhibition of acetyl-CoA carboxylase enzymes in a human, the method comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of structure:
or a pharmaceutically acceptable salt thereof, wherein the disease, condition or disorder is selected from the group consisting of Type I diabetes, Type II diabetes and diabetes-related diseases, nonalcoholic fatty liver disease (NAFLD), hepatic insulin resistance, hyperglycemia, metabolic syndrome, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, obesity, obesity-related disorders, dyslipidemia, hypertension, hyperinsulinemia, insulin resistance syndrome, atherosclerosis, coronary heart disease, coronary artery disease, heart failure, stroke, peripheral vascular disease, nephropathy, hypertension, neuropathy, and retinopathy.
2. The method of claim 1 , wherein disease, condition or disorder is nonalcoholic fatty liver disease (NAFLD).
3. The method of claim 1 , wherein disease, condition or disorder is type II diabetes.
4. The method of claim 1 , wherein disease, condition or disorder is obesity.
5. The method of claim 1 , wherein disease, condition or disorder is atherosclerosis.
6. The method of claim 1 , wherein disease, condition or disorder is coronary heart disease.
7. The method of claim 1 , wherein disease, condition or disorder is stroke.
8. The method of claim 1 , wherein disease, condition or disorder is heart failure.
9. The method of claim 1 , wherein disease, condition or disorder is hepatic insulin resistance.
10. A method for treating a disease, condition or disorder mediated by the inhibition of acetyl-CoA carboxylase enzymes in a human, the method comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a pharmaceutical composition comprising a compound of structure:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, diluent or carrier, wherein the disease, condition or disorder is selected from the group consisting of Type I diabetes, Type II diabetes and diabetes-related diseases, nonalcoholic fatty liver disease (NAFLD), hepatic insulin resistance, hyperglycemia, metabolic syndrome, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, obesity, obesity-related disorders, dyslipidemia, hypertension, hyperinsulinemia, insulin resistance syndrome, atherosclerosis, coronary heart disease, coronary artery disease, heart failure, stroke, peripheral vascular disease, nephropathy, hypertension, neuropathy, and retinopathy.