Patent NZ-599966-A (NZ)
Title: Novel compounds as receptor modulators with therapeutic utility
Inventor: HEIDELBAUGH TODD M
IPC: A61K31/397
Filed: 2010-11-19
Abstract: Disclosed are 1-(benzyl)azetidine-3-carboxylic acid and 3-benzylamino)cyclobutanecarboxylic acid derivatives as represented by the general formula (I), wherein: R1 is CH; R2 is an aromatic heterocycle, a non-aromatic heterocycle, cycloalkyl, cycloalkenyl or aryl, each of which is optionally substituted with one or more alkyl groups; R3 is O or S; R4 is optionally substituted aryl; R5 is H, halogen or alkoxy; R6 is H; R7 is H or alkyl; R8 is H; R9 is CH or N; R10 is carboxylic acid; a is 0, 1, 2 or 3; b is 0, 1, 2 or 3; c is 1; d is 0 or 1; e is 0; f is 1; g is 0; L is CH2, CH(alkyl) or O; and with the proviso that when R3 is O or S and b is 0 or 1 then L is not O. Representative compounds of formula I include 1-{ 3-(3-furyl)-4-[(5-phenylpentyl)oxy]benzyl} azetidine-3-carboxylic acid, 1-{ 3-chloro-4-[(5-phenylpentyl)oxy]-5-(2-thienyl)benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1,3-thiazol-5-yl)benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1,3-thiazol-4-yl)benzyl} azetidine-3-carboxylic acid, 1-{ 3-cyclopent-1-en-1-yl-4-[(5-phenylpentyl)oxy]benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(2-thienyl)benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1H-pyrazol-5-yl)benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1H-pyrazol-4-yl)benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(3-thienyl)benzyl} azetidine-3-carboxylic acid, 1-{ 3-(2-furyl)-4-[(5-phenylpentyl)oxy]benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1,3-thiazol-2-yl)benzyl} azetidine-3-carboxylic acid, 1-{ 3-(1,3-oxazol-2-yl)-4-[(5-phenylpentyl)oxy]benzyl} azetidine-3-carboxylic acid, 1-{ 4-[(5-phenylpentyl)oxy]-3-(1H-pyrazol-1-yl)benzyl} azetidine-3-carboxylic acid and 3-({ 4-[(5-phenylpentyl)oxy]-3-(2-thienyl)benzyl} amino)cyclobutane-carboxylic acid. Further disclosed is a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of a compound as defined above and a pharmaceutically acceptable adjuvant, diluent or carrier, for the treatment of ocular disease, wet and dry age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal edema, geographic atrophy, glaucomatous optic neuropathy, chorioretinopathy, hypertensive retinopathy, ocular ischemic syndrome, prevention of inflammation-induced fibrosis in the back of the eye, various ocular inflammatory diseases including uveitis, scleritis, keratitis, and retinal vasculitis; or systemic vascular barrier related diseases , various inflammatory diseases, including acute lung injury, its prevention, sepsis, tumor metastasis, atherosclerosis, pulmonary edemas, and ventilation-induced lung injury; or autoimmune diseases and immunosuppression, rheumatoid arthritis, Crohn’s disease, Graves’ disease, inflammatory bowel disease, multiple sclerosis, Myasthenia gravis, Psoriasis, ulcerative colitis, antoimmune uveitis, renal ischemia/perfusion injury, contact hypersensitivity, atopic dermatitis, and organ transplantation; or allergies and other inflammatory diseases , urticaria, bronchial asthma, and other airway inflammations including pulmonary emphysema and chronic obstructive pulmonary diseases; or cardiac protection , ischemia reperfusion injury and atherosclerosis; or wound healing, scar-free healing of wounds from cosmetic skin surgery, ocular surgery, GI surgery, general surgery, oral injuries, various mechanical, heat and burn injuries, prevention and treatment of photoaging and skin ageing, and prevention of radiation-induced injuries; or bone formation, treatment of osteoporosis and various bone fractures including hip and ankles; or anti-nociceptive activity, visceral pain, pain associated with diabetic neuropathy, rheumatoid arthritis, chronic knee and joint pain, tendonitis, osteoarthritis, neuropathic pains.