Patent ID: 8877786

Claim:
A method of treating a disorder or a disease associated with neutral endopeptidase EC. 3.4. 24.11. activity in a subject in need thereof, comprising: administering to the subject a therapeutically effective amount of a compound of the formula (I′): wherein: X 1 is OH, —O—C 1-7 alkyl, —NR a R b , —NHS(O) 2 —C 1-7 alkyl or —NHS(O) 2 -benzyl, wherein R a and R b for each occurrence are independently H or C 1-7 alkyl; R 1 is H, C 1-6 alkyl or C 6-10 -aryl-C 1-6 alkyl, wherein alkyl is optionally substituted with benzyloxy, hydroxy or C 1-6 alkoxy; for each occurrence, R 2 is independently C 1-6 -alkoxy, hydroxy, halo, C 1-6 -alkyl, cyano or trifluoromethyl; A 2 is O or NR 5 ; R 4 and R 5 are independently H or C 1-6 alkyl; A 1 is a bond or C 1-3 alkylene chain; R 3 is a 5- or 6-membered heteroaryl, C 6-10 -aryl or C 3-7 -cycloalkyl, wherein each heteroaryl, aryl or cycloalkyl are optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, halo, haloC 1-6 alkyl, C 1-6 alkoxy, hydroxy, CO 2 H and CO 2 C 1-6 alkyl; R 6 for each occurrence is independently halo, hydroxy, C 1-7 alkoxy, halo, C 1-7 alkyl or halo-C 1-7 alkyl; or R 4 , A 1 -R 3 , together with the nitrogen to which R 4 and A 1 -R 3 are attached, form a 4- to 7-membered heterocyclyl or a 5- to 6-membered heteroaryl, each of which is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, halo, haloC 1-6 alkyl, C 1-6 alkoxy, hydroxy, CO 2 H and CO 2 C 1-6 alkyl; and m is 0 or an integer from 1 to 5; s is 0 or an integer from 1 to 4; or a pharmaceutically acceptable salt thereof, wherein the disorder or disease is selected from, left ventricular hypertrophy, angina, renal insufficiency, renal failure, diabetic nephropathy, non-diabetic nephropathy, nephroic syndrome, glomerulonephritis, scleroderma, glomerular sclerosis, proteinurea of primary renal disease, renal vascular hypertention, diabetic retinopathy and end-stage renal disease (ESRD), endothelial dysfunction, diastolic dysfunction, hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation (AF), cardiac fibrosis, atrial flutter, detrimental vascular remodeling, plaque stabilization, myocardial infarction (MI), renal fibrosis, polycystic kidney disease (PKD), renal failure, cyclical oedema, Menières disease, hyperaldosteroneism hypercalciuria, ascites, glaucoma, menstrual disorders, preterm labour, pre-eclampsia, endometriosis, and reproductive disorders, asthma, obstructive sleep apnea, inflammation, leukemia, pain, epilepsy, affective disorders, depression, psychotic condition, dementia, geriatric confusion, obesity, gastrointestinal disorders, wound healing, septic shock, gastric acid secretion dysfunction, hyperreninaemia, cystic fibrosis, restenosis, type-2 diabetes, metabolic syndrome, diabetic complications, atherosclerosis, male and female sexual dysfunction.