Organic compounds

Abstract

New compounds of the Formula (I): for the treatment of non-insulin-dependent diabetes mellitus.

1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 X is ═N—; 
 Y is ═N—; 
 R 1  and R 2  are each independently selected from R 10 , —OR 10 , —C(O)R 10 , —C(O)OR 10  and —S(O) l R 10 ; 
 R 3  and R 4  are each independently hydrogen or R 13 ; or R 3  and R 4  taken together with the carbon atom to which they are attached form carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R 13 ; 
 R 5  is aryl or heteroaryl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R 13 ; 
 R 6  is selected from halogen, trifluoromethyl, cyano, nitro, R 10 , —C(O)R 10 , —C(O)R 10 , —OC(O)R 10 , —S(O) l R 11 , —N(R 11 )(R 12 ) and —C(O)N(R 11 )(R 12 ); 
 R 7 , R 8  and R 9  are each independently selected from hydrogen, halogen and moieties comprising from 1 to 30 plural valent atoms selected from C, N, O and S; for example R 7 , R 8  and R 9  are each independently selected from halogen, trifluoromethyl, cyano, nitro, R 10 , —OR 10 , —C(O)R 10 , —C(O)OR 10 , —OC(O)R 10 , —S(O) l R 11 , —N(R 11 )(R 12 ) and —C(O)N(R 11 )(R 12 ); 
 R 10  is hydrogen, hydrocarbyl optionally substituted with 1, 2, 3, 4 or 5 R 13 ; or —(CH 2 ) k -heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 13 ; 
 R 11  and R 12  are each independently selected from R 10 , —OR 10 , —C(O)R 10 , —C(O)OR 10 , —(CH 2 ) k —R 10 , —C(O)—(CH 2 ) k —R 10  and —S(O) l R 10 ; or R 11  and R 12  taken together with a nitrogen atom to which they are attached form heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 13 ; 
 each R 13  is independently selected from halogen, trifluoromethyl, cyano, nitro, oxo, ═NR 14 , —OR 14 , —C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 , —S(O) l R 14 , —N(R 14 )R 15 , —C(O)N(R 14 )R 15  and R 16 ; 
 R 14  and R 16  are each independently hydrogen or R 16 ; 
 R 16  is selected from a spiro group, hydrocarbyl, —(CH 2 ) k -hydrocarbyl, —(CH 2 ) k -heterocyclyl and —(CH 2 ) k —C(O)-heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen, cyano, oxo, amino, hydroxy, —C(O)—C 1-6  alkyl, C 1-6  alkyl and C 1-6  alkoxy; 
 j is 0, 1 or 2; 
 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. 
     
     
         2 . The compound according to  claim 1 , wherein;
 R 11  and R 12  are each independently selected from R 10 , —OR 10 , —C(O)R 10 , —C(O)OR 10  and —S(O) l R 10 ; or R 11  and R 12  taken together with a nitrogen atom to which they are attached form heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 13 ; and   R 16  is 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 halogen, cyano, amino, hydroxy, C 1-6  alkyl and C 1-6  alkoxy;   
       or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         3 . The compound according to  claim 1 , which is of the Formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         4 . The compound according to  claim 3 , wherein R 8  is hydrogen. 
     
     
         5 . The compound according to  claim 1 , which is of the Formula (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         6 . The compound according to  claim 1 , wherein R 1  and R 2  are each independently selected from hydrogen, C 1-6  alkyl optionally substituted with 1, 2, 3, 4 or 5 R 13 , and —(CH 2 ) k -carbocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 13 . 
     
     
         7 . The compound according to  claim 6 , wherein R 1  and R 2  are each hydrogen. 
     
     
         8 . The compound according to  claim 1 , wherein R 3  and R 4  are each independently selected from hydrogen, C 1-6  alkyl optionally substituted with 1, 2, 3, 4 or 5 R 13 , and —(CH 2 ) k -carbocyclyl optionally substituted with 1, 2, 3, 4 or 5 R 13 . 
     
     
         9 . The compound according to  claim 8 , wherein R 3  and R 4  are each hydrogen. 
     
     
         10 . The compound according to  claim 1 , wherein R 1 , R 2 , R 3  and R 4  are each hydrogen. 
     
     
         11 . The compound according to  claim 1 , wherein R 5  is aryl optionally substituted with 1, 2, 3, 4 or 5 R 13 . 
     
     
         12 . The compound according to  claim 11 , wherein R 5  is phenyl optionally substituted with 1, 2, 3, 4 or 5 R 13 . 
     
     
         13 . The compound according to  claim 12 , wherein R 5  is phenyl optionally substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, amino, hydroxy, C 1-6  alkyl and C 1-6  alkoxy. 
     
     
         14 . The compound according to  claim 13 , wherein R 5  is phenyl comprising substituents at the 2- and 4-positions, wherein the substituents are independently selected from halogen, methyl and methoxy. 
     
     
         15 . The compound according to  claim 14 , wherein R 5  is 2,4-dichlorophenyl. 
     
     
         16 - 63 . (canceled) 
     
     
         64 . The compound according to  claim 1 , selected from: 
       
         12 
         13 
         14 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or, in each case, a pharmaceutically acceptable salt, free form or prodrug thereof. 
     
     
         65 - 66 . (canceled) 
     
     
         67 . A pharmaceutical formulation, comprising;
 a compound of  claim 1 , and   a pharmaceutically acceptable excipient or carrier.   
     
     
         68 . (canceled) 
     
     
         69 . A formulation according to  claim 67 , which further comprises a therapeutic agent 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; or pharmaceutically acceptable salts or prodrugs thereof. 
     
     
         70 - 74 . (canceled) 
     
     
         75 . A method of treating or preventing a disease or condition 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 (such as Alzheimer's disease, Parkinson's disease, Crohn's disease or ulcerative colitis), hyperglycemia, insulin resistance, lipid disorders, dyslipidemia, hyperlipidennia, 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, diabetic cardiomyopathy, left or right ventricular hypertrophy, hypertrophic medial thickening in arteries and/or in large vessels, mesenteric vasculature hypertrophy, mesanglial hypertrophy, hypertension and osteoporosis, for producing a sedative or anxiolytic effect, attenuating post-surgical catabolic changes or hormonal responses to stress, reducing mortality and morbidity after myocardial infarction, modulating hyperlipidemia or associated conditions, or lowering VLDL, LDL or Lp(a) levels in a patient, comprising:
 administering a therapeutically effective amount of the compound of  claim 1 .   
     
     
         76 . (canceled)