Nitrogen-containing heterocyclic compounds and methods of use thereof

Abstract

The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, esters, and tautomers thereof, wherein: Q is selected from the group consisting of: and L is selected from the group consisting of: pharmaceutically compositions comprising one or more compounds of formula (I), and methods of using the compounds of formula (I).

1 . A compound having the formula: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt or solvate thereof, 
       wherein:
 R 1  is haloalkyl; and 
 R 2  is H or cycloalkyl. 
 
     
   
   
       2 . A compound having the formula: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt or solvate thereof, 
       wherein:
 R 1  and R 2  are each, independently, haloalkyl. 
 
     
   
   
       3 . The compound of  claim 1 , wherein R 1  is fluoroalkyl. 
   
   
       4 . The compound of  claim 2 , wherein R 1  is -alkylene-CF 2 . 
   
   
       5 . The compound of  claim 2 , wherein R 1  is -alkylene-F. 
   
   
       6 . The compound of  claim 4 , wherein R 1  is —(CH 2 ) 3 —CF 2 , —(CH 2 ) 4 —CF 2  or —(CH 2 ) 5 —CF 2 . 
   
   
       7 . The compound of  claim 1 , wherein R 2  is H. 
   
   
       8 . The compound of  claim 1 , wherein R 2  is cycloalkyl. 
   
   
       9 . The compound of  claim 8 , wherein R 2  is cyclobutyl. 
   
   
       10 . The compound of  claim 2 , wherein R 2  is H. 
   
   
       11 . The compound of  claim 3 , wherein R 2  is H. 
   
   
       12 . The compound of  claim 2 , wherein R 2  is cycloalkyl. 
   
   
       13 . The compound of  claim 3 , wherein R 2  is cycloalkyl. 
   
   
       14 . A compound having the structure: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
   
   
       15 . A composition comprising at least one compound of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       16 .- 38 . (canceled) 
   
   
       39 . A method of treating metabolic syndrome, dyslipidemia, a cardiovascular disease, a disorder of the peripheral and central nervous system, a hematological disease, cancer, inflammation, a respiratory disease, a gastroenterological disease, diabetes or non-alcoholic fatty liver disease in a patient, wherein the method comprises administering to the patient a therapeutically effective amount of at least one compound of  claim 1 , or a pharmaceutically acceptable salt, solvate, ester, or tautomer thereof. 
   
   
       40 . The method of  claim 39 , wherein the treating is for dyslipidemia. 
   
   
       41 . The method of  claim 39 , further comprising administering at least one additional therapeutic agent selected from the group consisting of hydroxy-substituted azetidinone compounds, substituted β-lactam compounds, HMG CoA reductase inhibitor compounds, HMG CoA synthetase inhibitors, squalene synthesis inhibitors, squalene epoxidase inhibitors, sterol biosynthesis inhibitors, nicotinic acid derivatives, bile acid sequestrants, inorganic cholesterol sequestrants, aspirin, NSAID agent, ezetimibe, Vytorin®, AcylCoA:Cholesterol O-acyltransferase inhibitors, cholesteryl ester transfer protein inhibitors, fish oils containing Omega 3 fatty acids, natural water soluble fibers, plant stanols and/or fatty acid esters of plant stanols, Omacor®, anti-oxidants, PPAR α agonists, PPAR γ-agonists, FXR receptor modulators, LXR receptor agonists, lipoprotein synthesis inhibitors, renin angiotensin inhibitors, microsomal triglyceride transport protein inhibitors, bile acid reabsorption inhibitors, PPAR δ agonists, triglyceride synthesis inhibitors, squalene epoxidase inhibitors, low density lipoprotein receptor inducers or activators, platelet aggregation inhibitors, 5-LO or FLAP inhibitors, PPAR δ partial agonists, niacin or niacin receptor agonists, 5HT transporter inhibitors, NE transporter inhibitors, CB 1  antagonists/inverse agonists, ghrelin antagonists, H 3  antagonists/inverse agonists, MCH1R antagonists, MCH2R agonists/antagonists, NPY1 antagonists, NPY5 antagonists, NPY2 agonists, NPY4 agonists, mGluR5 antagonists, leptins, leptin agonists/modulators, leptin derivatives, opioid antagonists, orexin receptor antagonists, BRS3 agonists, CCK-A agonists, CNTF, CNTF derivatives, CNTF agonists/modulators, 5HT2c agonists, Mc4r agonists, monoamine reuptake inhibitors, serotonin reuptake inhibitors, GLP-1 mimetics, phentermine, topiramate, phytopharm compound 57, ghrelin antibodies, Mc3r agonists, ACC inhibitors, β3 agonists, DGAT1 inhibitors, DGAT2 inhibitors, FAS inhibitors, PDE inhibitors, thyroid hormone β agonists, UCP-1 activators, UCP-2 activators, UCP-3 activators, acyl-estrogens, glucocorticoid agonists/antagonists, 11β HSD-1 inhibitors, SCD-1 inhibitors, lipase inhibitors, fatty acid transporter inhibitors, dicarboxylate transporter inhibitors, glucose transporter inhibitors, phosphate transporter inhibitors, antidiabetic agents, anti-hypertensive agents, anti-dyslipidemic agents, DPP-IV inhibitors, apolipoprotein-B secretion/microsomal triglyceride transfer protein (apo-B/MTP) inhibitors, sympathomimetic agonists, dopamine agonists, melanocyte-stimulating hormone receptor analogs, melanin concentrating hormone antagonists, leptons, galanin receptor antagonists, bombesin agonists, neuropeptide-Y antagonists, thyromimetic agents, dehydroepiandrosterone, analogs of dehydroepiandrosterone, urocortin binding protein antagonists, glucagons-like peptide-1 receptor agonists, human agouti-related proteins (AGRP), neuromedin U receptor agonists, noradrenergic anorectic agents, appetite suppressants, hormone sensitive lipase antagonists, MSH-receptor analogs, α-glucosidase inhibitors, apo A1 milano reverse cholesterol transport inhibitors, fatty acid binding protein inhibitors (FABP), and fatty acid transporter protein inhibitors (FATP). 
   
   
       42 . The method of  claim 41 , wherein the at least one additional active ingredient is an HMG CoA reductase inhibitor selected from: lovastatin, simvastatin, pravastatin, atorvastatin, fluvastatin, cerivastatin, rivastatin, rosuvastatin calcium, and pitavastatin. 
   
   
       43 . The method of  claim 41 , wherein the additional active ingredient is simvastatin. 
   
   
       44 .- 53 . (canceled)