Organic compounds

Abstract

The present invention relates to compounds of the formula; and their use in therapy.

1 .- 59 . (canceled) 
     
     
         60 . A method of treating or preventing a disease or condition in a patient, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein the asterisk * designates a chiral centre of (R) or (S) configuration; 
         V is absent or is ethylene; 
         W is —C(O)— or —S(O) 1 —; 
         X is a linker having 1 to 12 in-chain atoms and comprising one or more linkages selected from —O—, —C(O)—, —S(O) 1 —, —N(R 9 )— and hydrocarbylene, optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         Y is a linker selected from —O—, —N(R 9 )—, —C(O)—, —C(O)O—, —C(O)N(R 9 )—, —S(O) 1 — and S(O) 1 N(R 9 )—; 
         R 1  is selected from hydrogen; —N(R 9 )(R 10 ); hydrocarbyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; hydrocarbyloxy optionally substituted with 1, 2, 3, 4 or 5 R 11 ; and —(CH 2 ) k -heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         or, when Y is —N(R 9 )—, R 1  and R 9  taken together with the nitrogen atom to which they are attached may form a heterocycle, wherein said heterocycle is bound to X via said nitrogen atom and is optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         R 2  and R 3  are each independently selected from R 8 , —OR 8 , —C(O)R 8 , —C(O)OR 8  and —S(O) 1 R 9 ; 
         R 4  and R 5  are each independently selected from hydrogen, hydroxy, halogen and C 1-6  alkyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         R 6  is aryl or heteroaryl, either of which is optionally-substituted with 1, 2, 3, 4 or 5 R 11 ; 
         R 8  is selected from hydrogen; hydrocarbyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; and —(CH 2 ) k -heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         R 9  and R 10  are each independently selected from R 8 , —OR 8 , —C(O)R 8 , —C(O)OR 8  and —S(P) 1 R 8 ; 
         or R 9  and R 10  taken together with a nitrogen atom to which they are attached form heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 11 ; 
         each R 11  is independently selected from R 12 ; hydrocarbyl optionally substituted with 1, 2, 3, 4 or 5 R 12 ; and —(CH 2 ) k -heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 12 ; 
         R 12  is independently selected from halogen, trifluoromethyl, cyano, nitro, oxo, ═NR 13 , —OR 13 , —C(O)R 13 , —C(O)N(R 13 )R 14 , —C(O)OR 13 , —OC(O)R 13 , —S(O) 1 R 13 , —S(O) 1 N(R 13 )R 14 , —N(R 13 )R 14 , —N(R 13 )N(R 13 )R 14 , —N(R 13 )C(O)R 14  and —N(R 13 )S(O) 1 R 13 ; 
         R 13  and R 14  are each independently hydrogen or selected from hydrocarbyl and —(CH 2 ) k -heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from oxo, halogen, cyano, amino, hydroxy, C 1-6  alkyl and C 1-6  alkoxy; 
         k is 0, 1, 2, 3, 4, 5 or 6; and 
         l is 0, 1 or 2; 
         or a pharmaceutically acceptable salt or prodrug thereof; 
         thereby treating or preventing said disease or condition. 
       
     
     
         61 . The method of  claim 60 , wherein the compound is of the Formula (II): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         62 . The method of  claim 60 , wherein the compound is the Formula (III): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         63 . The method of  claim 60 , wherein X is —X 1 — and wherein X 1  is selected from —O—, —C(O)—, —S(O) 1 —, —N(R 9 )— and hydrocarbylene optionally substituted with 1, 2, 3, 4 or 5 R 11 . 
     
     
         64 . The method of  claim 63 , wherein the compound is of the Formula (IV): 
       
         
           
           
               
               
           
         
       
       wherein X 1  is —N(R 9 )— or hydrocarbylene optionally substituted with 1, 2, 3, 4 or 5 R 11 ;
 or a pharmaceutically acceptable salt or prodrug thereof. 
 
     
     
         65 . The method of  claim 60 , wherein said disease or condition is selected from non-insulin-dependent diabetes mellitus, arthritis, obesity, allograft transplantation, calcitonin-osteoporosis, heart failure, impaired glucose metabolism or impaired glucose tolerance, neurodegenerative diseases, cardiovascular or renal diseases, and neurodegenerative or cognitive disorders, hyperglycemia, insulin resistance, lipid disorders, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, high LDL levels, atherosclerosis, vascular restenosis, irritable bowel syndrome, inflammatory bowel disease, pancreatitis, retinopathy, nephropathy, neuropathy, syndrome X, ovarian hyperandrogenism (polycystic ovarian syndrome), type 2 diabetes, growth hormone deficiency, neutropenia, neuronal disorders, tumor metastasis, benign prostatic hypertrophy, gingivitis, hypertension and osteoporosis. 
     
     
         66 . The method of  claim 65 , wherein said disease or condition is Alzheimer's disease, Parkinson's disease, Crohn's disease or ulcerative colitis. 
     
     
         67 . The method of  claim 65 , wherein said disease or condition is diabetic cardiomyopathy, left or right ventricular hypertrophy, hypertrophic medial thickening in arteries and/or in large vessels, mesenteric vasculature hypertrophy or mesanglial hypertrophy. 
     
     
         68 . The method of  claim 60 , further comprising administering said compound in combination with one or more additional therapeutic agents selected from anti-diabetic agents, hypolipidemic agents, anti-obesity or appetite-regulating agents, anti-hypertensive agents, HDL-increasing agents, cholesterol absorption modulators, Apo-A1 analogues and mimetics, thrombin inhibitors, aldosterone inhibitors, inhibitors of platelet aggregation; estrogen, testosterone, selective estrogen, receptor modulators, selective androgen receptor modulators, chemotherapeutic agents, and 5-HT 3  or 5-HT 4  receptor modulators. 
     
     
         69 . The method of  claim 60 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         70 . The method according to  claim 60 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof.