| abstract |
Disclosed is a 1,3 disubstituted indole having the chemical structure (I) and all pharmaceutically acceptable salts, tautomers and stereoisomers thereof, wherein: D is methylene or sulphone; R34, R35, R36, R37, R38, R39, R40, R41, R30 and R31, R29, R32, R27 and R28, R43 are defined in the specification. R60 and R61 are each hydrogen; A is arylene or heteroarylene, wherein arylene or heteroarylene, T is a covalent bond, -O- or -C(=O)-; B is selected from the group consisting of aryl and heteroaryl; p is 1,2 or 3; n is 1, or 2 and Z is O or S. Also disclosed is the use of said indoles to treat a PPAR mediated disease e.g. obesity, overweight condition, bulimia, anorexia nervosa, hyperlipidemia, dyslipidemia, hypoalphalipoproteinemia, hypertriglyceridemia, hypercholesterolemia, low HDL, Metabolic Syndrome, Type II diabetes mellitus, Type I diabetes, hyperinsulinemia, impaired glucose tolerance, insulin resistance, a diabetic complication of neuropathy, nephropathy, retinopathy, diabetic foot ulcer or cataracts, hypertension, coronary heart disease, heart failure, congestive heart failure, atherosclerosis, arteriosclerosis, stroke, cerebrovascular disease, myocardial infarction, peripheral vascular disease, vitiligo, uveitis, pemphigus foliaceus, inclusion body myositis, polymyositis, dermatomyositis, scleroderma, Grave's disease, Hashimoto's disease, chronic graft versus host disease, rheumatoid arthritis, inflammatory bowel syndrome, Crohn's disease, systemic lupus erythematosis, Sjogren's Syndrome, multiple sclerosis, asthma, chronic obstructive pulmonary disease, polycystic kidney disease, polycystic ovary syndrome, pancreatitis, nephritis, hepatitis, eczema, psoriasis, dermatitis, impaired wound healing, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, acute disseminated encephalomyelitis, Guillain-Barre syndrome, thrombosis, infarction of the large or small intestine, renal insufficiency, erectile dysfunction, urinary incontinence, neurogenic bladder, ophthalmic inflammation, macular degeneration, pathologic neovascularization, HCV infection, HIV infection, Helicobacter pylori infection, neuropathic or inflammatory pain, infertility, and cancer. |