CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation-In-Part (CIP) of U.S. application Ser. No. 12/155,984, filed on Jun. 12, 2008, which is a CIP of U.S. application Ser. No. 10/983,227, filed on Nov. 8, 2004, which claims priority to Korean Application No. 10-2004-0027591, filed on Apr. 21, 2004. These applications are incorporated fully herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Technical Field of the Invention 
     This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and/or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors. 
     2. Background of the Invention 
     TGF-β denotes a family of proteins, TGF-β1, TGF-β2 and TGF-β3, which are pleiotropic modulators of cell proliferation and differentiation, wound healing, extracellular matrix production and immunosuppression. Other members of this superfamily include activins, inhibins, bone morphogenetic proteins, growth and differentiation factors and Müllerian inhibiting substance. 
     TGF-β1 transduces signals through two highly conserved single transmembrane serine/threonine kinases, the type I (ALK5) and type II TGF-β receptors. Upon ligand induced oligomerization, the type II receptor hyperphosphorylates serine/threonine residues in the GS region of the ALK5, which leads to activation of the ALK5 by creating a binding site for Smad proteins. The activated ALK5 in turn phosphorylates Smad2 and Smad3 proteins at the C-terminal SSXS-motif thereby causing their dissociation from the receptor and heteromeric complex formation with Smad4. Smad complexes translocate to the nucleus, assemble with specific DNA-binding co-factors and co-modulators to finally activate transcription of extracellular matrix components and inhibitors of matrix-degrading proteases. 
     Activins transduce signals in a manner similar to TGF-β. Activins bind to serine/thereonine kinase, the activin type II receptor (ActRIIB), and the activated type II receptor hyperphosphorylates serine/threonine residues in the GS region of the ALK4. The activated ALK4 in turn phosphorylates Smad2 and Smad3. The consequent formation of a hetero-Smad complex with Smad4 results in the activin-induced regulation of gene transcription. 
     Numerous experimental animal studies demonstrate an association between glomerular expression of TGF-β and fibrosis, including the Thy-1 rat model of proliferative glomerulonephritis, anti-GBM glomerulonephritis in rabbits, and the ⅚ nephrectomy rat model of focal segmental glomerulosclerosis, as has been reviewed recently (e.g., Bitzer, M. et al.,  Kidney Blood Press. Res.  21:1-12 (1998)). Neutralizing antibody to TGF-β improves glomerular histology in the Thy-1 nephritis model (e.g., Border, W. A. et al.,  Nature  346: 371-374 (1990)). 
     Hyperglycemic conditions increase TGF-β mRNA and protein synthesis in both murine proximal tubule cells and human mesangial cells (e.g., Wahab, N. A. et al.,  Biochem. J.  316:985-992 (1996); Rocco, M. V. et al.,  Kidney Int.  41: 107-114 (1992)). Diabetic patients with early kidney disease show increased accumulation of TGF-β mRNA and protein within the glomerulus (e.g., Yoshioka, K. et al.,  Lab. Invest.  68: 154-163 (1993)). In kidneys with chronic renal interstitial fibrosis, the hallmarks are thickened tubular basement membranes and an expanded interstitial compartment, with interstitial fibrosis characterized by an increase in collagens I, III, V, VII, and fibronectin (e.g., Eddy, A. A.,  J. Am. Soc. Nephrol.  7: 2495-2508 (1996)). 
     TGF-β gene expression and protein production are increased in a variety of animal models of pulmonary fibrosis including bleomycin, silica, asbestos, and radiation (e.g., Phan, S. H. and Kunkel, S. L.,  Exp. Lung Res.  18: 29-43 (1992); Williams, A. O. et al.,  Am. J. Pathol.  142: 1831-1840 (1993); Rube, C. E. et al.,  Int. J. Radiat. Oncol. Biol. Phys.  47: 1033-1042 (2000)). Coincident increase in TGF-β1 protein and collagen gene expression in adjacent tissue slices from idiopathic pulmonary fibrosis is observed in human pulmonary fibrotic disease (e.g., Broekelmann, T. J. et al.,  Proc. Natl. Acad. Sci. USA  88:6642-6646 (1991)). Increased TGF-β production has been documented in patients with sarcoidosis, pneumoconiosis, asbestosis, and radiation-induced fibrosis (e.g., Khalil, N. et al.,  Am. J. Respir. Cell. Mol. Biol.  14:131-138 (1996); Jagirdar, J. et al.,  Environ. Health Perspect.  105:1197-1203 (1997)). Anti-TGF-β antibodies and TGF-β-soluble receptors could partially inhibit fibrosis in bleomycin-induced lung fibrosis rodent models (e.g., Giri, S. N. et al.,  Thorax  48: 959-966 (1993); Wang, Q. et al.,  Thorax  54: 805-812 (1999)). Tobacco smoke has been implicated as one of the most important factors that can cause small airway disease followed by chronic obstructive pulmonary disease (COPD) (e.g., Wright, J. M. et al.,  Am. Rev. Respir. Dis.  146: 240-262 (1992)). COPD is a slowly progressive and irreversible disorder characterized by the functional abnormality of airway obstruction. TGF-β has been hypothesized to be involved in airway remodeling found in chronic airway inflammatory disorders such as COPD (e.g., Takizawa, H. Int.  J. Mol. Med.  1: 367-378 (1998); Ning, W. et al.,  Proc. Natl. Acad. Sci. USA  101:14895-14900 (2004)). 
     Hepatic stellate cells (HSC) are the major source of extracellular matrix proteins in hepatic fibrosis. Extracellular matrix production by activated hepatic stellate cells is markedly increased through the action of TGF-β1 (e.g., Friedman, S. L.,  Prog. Liver Dis.  14: 101-130 (1996); Pietrangelo, A.,  Semin. Liver Dis.  16:13-30 (1996)). Transgenic mice that overexpress TGF-β1 in the liver develop hepatic fibrosis as well as extrahepatic pathologies such as renal fibrosis (e.g., Sanderson, N. et al.,  Proc. Natl. Acad. Sci. USA  92:2572-2576 (1995)). 
     TGF-β1 and its receptors are overexpressed in injured blood vessels and in fibroproliferative vascular lesions leading to overproduction of extracellular matrix (e.g., Saltis, J. et al.,  Clin. Exp. Pharmacol. Physiol.  23: 193-200 (1996); McCaffrey, T. A. et al.,  J. Clin. Invest.  96: 2667-2675 (1995)). 
     Anti-TGF-β antibodies reduce scar formation and improve the cytoarchitecture of the neodermis in rats (e.g., Shah, M.,  J. Cell. Sci.  108: 985-1002 (1995)), improve healing of corneal wounds in rabbits (e.g., Moller-Pedersen, T.,  Curr. Eye Res.  17:736-747 (1998)), and accelerate wound healing of gastric ulcers in rats (e.g., Ernst, H.,  Gut  39: 172-175 (1996)). 
     Radiation fibrosis is a frequent sequel of therapeutic or accidental radiation overexposure in normal human tissues. TGF-β1 plays a central role in the initiation, development, and persistence of radiation fibrosis, as has been reviewed recently (e.g., Martin, M. et al.,  Int. J. Radiat. Oncol. Biol. Phys.  47:277-290 (2000)). 
     Organ transplantation is complicated in many instances by chronic rejection and for some organs such as the kidney, it is the major forms of graft loss. In human patients, chronic rejection of lung and kidney transplants is associated with increased expression of TGF-β within the tissue (e.g., El-Gamel, A. et al.,  Eur J. Cardiothorac. Surg.  13: 424-430 (1998); Shihab, F. S. et al.,  J. Am. Soc. Nephrol.  6:286-294 (1995)). 
     TGF-β is implicated in peritoneal adhesions (e.g., Saed, G. M. et al.,  Wound Repair Regeneration  7: 504-510 (1999)). The peritoneal and sub-dermal fibrotic adhesions could be prevented by inhibitors of ALK5 and/or ALK4. 
     The tumor cells and the stromal cells within the tumors in late stages of various cancers generally overexpress TGF-β. This leads to stimulation of angiogenesis and cell motility, suppression of the immune system, and increased interaction of tumor cells with the extracellular matrix (e.g., Hojo, M. et al.,  Nature  397: 530-534 (1999)). Consequently, the tumor cells become more invasive and metastasize to distant organs (e.g., Maehara, Y. et al.,  J. Clin. Oncol.  17: 607-614 (1999); Picon, A. et al.,  Cancer Epidemiol. Biomarkers Prev.  7:497-504 (1998)). 
     Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of both tissue-type plasminogen activator and urokinase-type plasminogen activator. Elevated levels of PAI-1 are associated with thrombosis and vascular disease, suggesting that high plasma PAI-1 may promote a hypercoagulable state by disrupting the natural balance between fibrinolysis and coagulation (e.g., Vaughan, D. E.,  J. Invest. Med.  46: 370-376 (1998)). It is known that TGF-β stimulates the expression of PAI-1 (e.g., Dennler, S. et al.,  EMBO J.  17: 3091-3100 (1998)). Accordingly, inhibition of the production of PAI-1 with an inhibitor of the TGF-β signaling pathway could produce a novel fibrinolytic therapy. 
     Activin signaling and overexpression of activin is linked to pathological disorders that involve extracellular matrix accumulation and fibrosis (e.g., Matsuse, T. et al.,  Am. J. Respir Cell MoL Biol.  13:17-24 (1995); Inoue, S. et al.,  Biochem. Biophys. Res. Comm.  205:441-48 (1994); Matsuse, T. et al.,  Am. J. Pathol.  148:707-713 (1996); De Bleser et al.,  Hepatology  26:905-912 (1997); Pawlowski, J. E., et al.,  J. Clin. Invest.  100:639648 (1997); Sugiyama, M. et al.,  Gastroenterology  114:550-558 (1998); Munz, B. et al.,  EMBO J.  18:5205-5215 (1999)), inflammatory responses (e.g., Rosendahl, A. et al.,  Am. J. Respir Cell Mol. Biol.  25:60-68 (2001), cachexia or wasting (Matzuk, M. M. et al.,  Proc. Natl. Acd. Sci. USA  91:8817-8821 (1994); Coerver, K. A. et al.,  Mol. Endocrinol.  10:534-543 (1996); Cipriano, S. C. et al.,  Endocrinology  141:2319-2327 (2000)), diseases or pathological responses in the central nervous system (e.g., Logan, A. et al.,  Eur J. Neurosci.  11:2367-2374 (1999); Logan, A. et al.,  Exp. Neurol.  159:504-510 (1999); Masliah, E. et al.,  Neurochem. Int.  39:393-400 (2001); De Groot, C. J. A. et al.,  J. Neuropathol. Exp. Neurol.  58:174-187 (1999); John, G. R. et al.,  Nat. Med.  8:1115-1121 (2002)) and hypertension (e.g., Dahly, A. J. et al.,  Am. J. Physiol. Regul. Integr. Comp. Physiol.  283: R757-767 (2002)). Studies have shown that TGF-β and activin can act synergistically to induce extracellular matrix production (e.g., Sugiyama, M. et al.,  Gastroenterology  114; 550-558 (1998)). 
     Therefore, it becomes evident that inhibition of ALK5 and/or ALK4 phosphorylation of Smad2 and Smad3 by the preferred compounds of this invention could treat and prevent disorders involving these signaling pathways. 
     WO 00/61576 and US 2003/0149277 A1 disclose triarylimidazole derivatives and their use as ALK5 inhibitors. WO 01/62756 A1 discloses pyridinylimidazole derivatives and their use as ALK5 inhibitors. WO 02/055077 A1 discloses use of imidazolyl cyclic acetal derivatives as ALK5 inhibitors. And, also, WO 03/087304 A2 discloses tri-substituted heteroaryls and their use as ALK5 and/or ALK4 inhibitors. 
     SUMMARY OF THE INVENTION 
     Surprisingly, it has now been discovered that a class of 2-pyridyl substituted imidazoles function as potent and selective inhibitors of ALK5 and/or ALK4 and therefore, have utility in the treatment and prevention of various disease states mediated by ALK5 and/or ALK4, such as glomerulonephritis, diabetic nephropathy, lupus nephritis, hypertension-induced nephropathy, renal interstitial fibrosis, renal fibrosis resulting from complications of drug exposure, HIV-associated nephropathy, transplant necropathy, liver fibrosis due to all etiologies, hepatic dysfunction attributable to infections, alcohol-induced hepatitis, disorders of the biliary tree, pulmonary fibrosis, acute lung injury, adult respiratory distress syndrome, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, pulmonary disease due to infectious or toxic agents, post-infarction cardiac fibrosis, congestive heart failure, dilated cardiomyopathy, myocarditis, vascular stenosis, restenosis, atherosclerosis, ocular scarring, corneal scarring, proliferative vitreoretinopathy, excessive or hypertrophic scar or keloid formation in the dermis occurring during wound healing resulting from trauma or surgical wounds, peritoneal and sub-dermal adhesion, scleroderma, fibrosclerosis, progressive systemic sclerosis, dermatomyositis, polymyositis, arthritis, osteoporosis, ulcers, impaired neurological function, male erectile dysfunction, Peyronie&#39;s disease, Dupuytren&#39;s contracture, Alzheimer&#39;s disease, Raynaud&#39;s syndrome, fibrotic cancers, tumor metastasis growth, radiation-induced fibrosis, and thrombosis. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The aforementioned aspects and other features of the present invention will be explained in the following description, taken in conjunction with the accompanying drawings, wherein: 
         FIG. 1  shows effect of the compounds of Examples 32, 45, 73, 79, and 83 on TGF-β1-induced 3TP-Luc reporter activity in HepG2 cells. 
     
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     In an embodiment of the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt thereof: 
     
       
                 
         
             
             
         
      
     
     wherein R 1  is naphthyl, anthracenyl, or phenyl optionally substituted with substituents selected from halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloalkyl, —O—(CH 2 ) n -Ph, —S—(CH 2 ) n -Ph, cyano, phenyl, and CO 2 R, wherein R is H or C 1-6 alkyl, and n is 0, 1, 2, or 3; or R 1  is phenyl or pyridyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S, and the fused phenyl or pyridyl may be further optionally substituted by halo, OH, —O—C 1-6 alkyl, —S—C 1-6  alkyl, C 1-6 alkyl, C 1-6 haloalkyl, cyano, phenyl or ═O; is H, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, phenyl, C 1-6 haloalkyl, NH 2 , NH(CH 2 ) n -Ph, NH—C 1-6 alkyl, halo, CN, NO 2 , CONHR or SO 2 NHR, wherein R is H or C 1-6 alkyl, and ni s 0, 1, 2, or 3; 
     R 3  is 
                                
or R 3  heteroaromatic cyclic ring optionally substituted with substituents selected from halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloalkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, —O—(CH 2 ) n -Ph, —S—(CH 2 ) n -Ph, cyano, phenyl, and CO 2 R, wherein R is H or C 1-6 alkyl, and n is 0, 1, 2, or 3; or R 3  is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S, and the fused phenyl may be further optionally substituted by halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloalkyl, cyano, or phenyl;
 
     R 4  is halo, C 1-6 haloalkyl, —SO 2 C 1-6 alkyl or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S; 
     R 5  and R 6  are independently H, halo, C 1-6 alkyl, C 3-7 cycloalkyl, —(CH 2 ) p —NO 2 , —(CH 2 ) p —NR 7 R 8 , —(CH 2 ) p —CHO, —(CH 2 ) p —CONHOH, —(CH 2 ) p —CN, —(CH 2 ) p —CO 2 H, —(CH 2 ) p —CO 2 R 7 , —(CH 2 ) p —CONR 7 R 8 , —(CH 2 ) p —C(═NR 7 )NR 7 R 8 , —(CH 2 ) p -tetrazole, —(CH 2 ) p —COR 7 , —(CH 2 ) q —(OR 9 ) 2 , —(CH 2 ) p —OR 7 , —(CH 2 ) p —CH═CH—CN, —(CH 2 ) p —CH═CH—CO 2 H, —(CH 2 ) p —CH═CH—CO 2 R 7 , —(CH 2 ) p —CH═CH—CONR 7 R 8 , —(CH 2 ) p —NHCOR 7 , —(CH 2 ) p —NHCO 2 R 7 , —(CH 2 ) p —CONHSO 2 R 7 , —(CH 2 ) p —NHSO 2 R 7  or —(CH 2 ) p —CH═CH-tetrazole; 
     R 7  and R 8  are independently H, phenyl or C 1-6 alkyl wherein phenyl or C 1-6 alkyl is optionally substituted by —(CH 2 ) q —CONHOH, —(CH 2 ) q —CN, —(CH 2 ) q —CO 2 R 10 , —(CH 2 ) q —CONR 11 R 12 , —(CH 2 ) q -tetrazole, —(CH 2 ) r —OR 10 , —(CH 2 ) r —R 13 , —(CH 2 ) r —NR 11 R 12 ; or R 7  and R 8  are taken together to form non-aromatic cyclic ring of 3-6 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S; 
     R 9  is C 1-6 alkyl; 
     R 10 , R 11  and R 12  are independently H or C 1-6 alkyl; 
     R 13  is 3-7 membered heterocyclic ring optionally substituted at one, two or three positions by halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloalkyl, amino, C 1-6 alkylamino, di(C 1-6  alkyl)amino, cyano, oxo, carboxy or nitro; 
     p is 0, 1, 2, 3, or 4; 
     q is 1, 2, 3, or 4; 
     r is 2, 3, or 4; 
     X is C 1-10 alkylene, C 2-10 alkenylene or C 2-10 alkynylene; 
     one of A 1  and A 2  is N and the other is NR 14 ; and 
     R 14  is H, OH, C 1-6 alkyl, or C 3-7 cycloalkyl. 
     As used herein, the double bond indicated by the dotted lines of formula (I), represent the possible tautomeric ring forms of the compounds falling within the scope of this invention, the double bond being to the unsubstituted nitrogen. 
     Preferably, R 1  is naphthyl or phenyl optionally substituted with substituents selected from halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, and phenyl; or R 1  is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to two heteroatoms, independently selected from N, O and S, and the fused phenyl ring may be further optionally substituted by halo, OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl or C 1-6 haloalkyl. For example, R 1  represents benzo[1,3]dioxolyl, 2,3-dihydrobenzo[1,4]dioxinyl, benzoxazolyl, benzothiazolyl, benzo[1,2,5]oxadiazolyl, benzo[1,2,5]thiadiazolyl, quinoxalin-6-yl, quinolin-6-yl, dihydrobenzofuranyl, benzimidazolyl, C 1-6 benzimidazolyl, benzoxazolyl-2-one or benzo[1,4]oxazinyl. 
     Preferably, R 2  is other than H. When R 2  is other than H, it is preferably positioned ortho to the nitrogen of the pyridyl ring. R 2  is preferably C 1-4  alkyl. 
     Preferably, R 3  is 
                                
or R 3  is heteroaromatic cyclic ring optionally substituted with substituents selected from halo, OH, —O—C 1-3 alkyl, C 1-3 alkyl, C 1-3 haloalkyl, amino, C 1-3  alkylamino, di(C 1-3 alkyl)amino, cyano, carboxy, and CO 2 R, wherein R is H or C 1-3 alkyl; or R 3  is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-6 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S, and the fused phenyl may be further optionally substituted by halo, —O—C 1-3 alkyl, C 1-3 alkyl, C 1-3 haloalkyl, cyano.
 
     Preferably, R 4  is halo, C 1-3 haloalkyl, —SO 2 C 1-6 alkyl or non-aromatic cyclic ring of 5-6 members wherein said cyclic ring optionally contains up to two heteroatoms, independently selected from N and O; 
     Preferably, R 5  and R 6  are independently H, halo, —(CH 2 ) p —NO 2 , —(CH 2 ) p —NR 7 R 8 , —(CH 2 ) p —CN, —(CH 2 ) p —CO 2 H, —(CH 2 ) p —CO 2 R 7 , —(CH 2 ) p —CONR 7 R 8 , —(CH 2 ) p —OR 7 . 
     Preferably, R 7  and R 8  are independently H, phenyl or C 1-6 alkyl wherein phenyl or C 1-6 alkyl is optionally substituted by —(CH 2 ) q —CO 2 R 10 , —(CH 2 ) q —CONR 11 R 12 , —(CH 2 ) r —OR 10 , —(CH 2 ) r —R 13 , —(CH 2 ) r —NR 11 R 12 , or R 7  and R 8  are to form non-aromatic cyclic ring of 3-6 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S; 
     Preferably, R 10 , R 11  and R 12  are independently H or C 1-3 alkyl. 
     Preferably, R 13  is 3-6 membered heterocyclic ring. 
     Preferably, p is 0, 1, or 2. 
     Preferably, q is 1, 2, or 3. 
     Preferably, r is 2 or 3. 
     Preferably, X is C 1-6 alkylene. 
     Preferably, one of A 1  and A 2  is N and the other is NR 14 , wherein R 14  is H. 
     Specific compounds of the invention which may be mentioned include the following and pharmaceutically acceptable salts or hydrates thereof:
     6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(3-(methylsulfonyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-fluorobenzyl)-1H-imidazol-4-yl)quinoline   6-(2-(3-bromobenzyl)-5-(6-bromopyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-chlorobenzyl)-1H-imidazol-4-yl)quinoline   2-methyl-6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(3-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   2-methyl-6-(5-(6-methylpyridin-2-yl)-2-(3-(methylsulfonyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)-2-methylquinoline   6-(2-(3-bromobenzyl)-5-(6-bromopyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-chlorobenzyl)-1H-imidazol-4-yl)-2-methylquinoline   6-(5-(6-bromopyridin-2-yl)-2-(3-fluorobenzyl)-1H-imidazol-4-yl)-2-methylquinoline   2-(4-(4-methoxyphenyl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(2-(3-chlorobenzyl)-4-(4-methoxyphenyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(4-(4-chlorophenyl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(4-(4-chlorophenyl)-2-(3-fluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-chlorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-fluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-chloropyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(3-chlorobenzyl)-5-(6-chloropyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-chloro-6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(2-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-4-yl)quinoline   6-(2-(2-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-methylpyridin-2-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3,4-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-bromo-4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(3,5-bis(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(4-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3,5-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(2,3-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(4-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-fluoro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-chloro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(2,3-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3,4-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3,5-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(2-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(4-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-methylpyridin-2-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3,5-bis(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-bromo-4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-fluoro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(4-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(2,3-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(2,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-chloro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoxaline   6-(2-(3-bromo-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   6-(5-(6-methylpyridin-2-yl)-2-(3-phenoxybenzyl)-1H-imidazol-4-yl)quinoxaline   6-(2-(2-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(2,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(3-bromo-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline   6-(2-(4-chloro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-chloro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   6-(2-(4-fluoro-3-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol   6-(2-((6-chloropyridin-3-yl)methyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(pyridin-3-ylmethyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoline   6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoxaline   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)-N,N-dimethylethanamine   6-(2-(4-fluoro-3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   4-(2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethyl)morpholine   3-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)-N,N-dimethylpropan-1-amine   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenylamino)ethanol   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanol   6-(2-(4-fluoro-3-(2-methoxyethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   Methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanol   6-(2-(4-fluoro-3-(2-methoxyethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanamine   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetamide   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetic acid   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanamine   methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetic acid   2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetamide   6-(2-((6-chloropyridin-2-yl)methyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzoic acid   6-(2-(4-fluoro-3-(1H-tetrazol-5-yl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   2-fluoro-N-(2-methoxyethyl)-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   2-fluoro-N-(2-hydroxyethyl)-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanamine   (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanol   6-(5-(6-methylpyridin-2-yl)-2-(3-(pyrrolidin-1-yl)benzyl)-1H-imidazol-4-yl)quinoline   6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)aniline   6-(5-(6-methylpyridin-2-yl)-2-(pyridin-2-ylmethyl)-1H-imidazol-4-yl)quinoline   6-(2-(4-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(4-bromobenzyl)-5-(pyridin-2-yl)-1H-imidazol-4-yl)quinoline   6-(2-(4-bromobenzyl)-5-(6-methoxypyridin-2-yl)-1H-imidazol-4-yl)quinoline;
 
and a pharmaceutically acceptable salt or hydrate thereof.
   

     The compounds of the present invention typically are small organic molecules (non-peptide small molecules), generally less than about 1,000 daltons in size. Preferred non-peptide small molecules have molecular weights of less than about 750 daltons, more preferably less than about 500 daltons, and even more preferably less than about 300 daltons. 
     Compounds of formula (I) may also be supplied in the form of a “prodrug” which is designed to release compound of formula (I) when administered to a subject. Prodrug formed designs are well known in the art, and depend on the substituents contained in compound of formula (I). For example, a substituent containing hydroxyl could be coupled to a carrier which renders the compound biologically inactive until it is removed by endogenous enzymes or, for example, by enzymes targeted to a particular receptor or location in the subject. 
     A compound of formula (I) that is acidic in nature (e.g., having a carboxyl or phenolic hydroxyl group) can form a pharmaceutically acceptable salt such as a sodium, potassium, calcium, or gold salt. Also within the scope of the invention are salts formed with pharmaceutically acceptable amines such as ammonia, alkyl amines, hydroxyalkylamines, and N-methylglycamine. A compound of formula (I) can be treated with an acid to form acid addition salts. Examples of such acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, methanesulfonic acid, phosphoric acid, p-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, oxalic acid, malonic acid, salicylic acid, malic acid, fumaric acid, ascorbic acid, maleic acid, acetic acid, and other mineral and organic acids well known to those skilled in the art. The acid addition salts can be prepared by treating a compound of formula (I) in its free base form with a sufficient amount of an acid (e.g., hydrochloric acid) to produce an acid addition salt (e.g., a hydrochloride salt). The acid addition salt can be converted back to its free base form by treating the salt with a suitable dilute aqueous basic solution (e.g., sodium hydroxide, sodium bicarbonate, potassium carbonate, or ammonia). 
     Some of the compounds of this invention may be crystallized or recrystallized from solvents such as aqueous and organic solvents. In such cases solvates may be formed. This invention includes within its scope stoichiometric solvates including hydrates as well as compounds containing variable amounts of water that may be produced by processes such as lyophilization. 
     Compounds of formula (I) may contain one or more asymmetric centers and thus can exist as enantiomers or diastereomers. It is to be understood that the invention includes both mixtures and separate individual isomers of compounds of the formula (I). Furthermore, certain compounds of the formula (I) which contain alkenyl groups may exist as cis- or trans-isomers. In each instance, the invention includes both mixtures and separate individual isomers. 
     Compounds of formula (I) may also exist in tautomeric forms and the invention includes both mixtures and separate individual tautomers thereof. 
     Also included in the invention are radiolabelled derivatives of compounds of formula (I) which are suitable for biological studies. 
     As used herein, the term “alkyl” group refers to a saturated aliphatic hydrocarbon group containing 1-10 (e.g., 1-6 or 1-4) carbon atoms. An alkyl group can be straight or branched. Examples of an alkyl group include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-heptyl, and 2-ethylhexyl. An alkyl group can be optionally substituted with one or more substituents such as alkoxy, cycloalkoxy, amino, nitro, carboxy, cyano, halo, hydroxy, sulfo, or mercapto. 
     As used herein, the term “alkylene” group refers to a saturated aliphatic hydrocarbon group containing 1-10 (e.g., 1-6 or 1-4) carbon atoms. An alkylene group can be straight or branched. Examples of an alkylene group include, but are not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, n-pentylene, n-heptylene, and 2-ethylhexylene. An alkylene group can be optionally substituted with one or more substituents such as alkoxy, cycloalkoxy, amino, nitro, carboxy, cyano, halo, hydroxy, sulfo, or mercapto. 
     As used herein, the term “alkenylene” group refers to an aliphatic carbon group that contains 2-10 (e.g., 2-6 or 2-4) carbon atoms and at least one double bond. Like an alkylene group, an alkenylene group can be straight or branched. Examples of an alkenylene group include, but are not limited to, allylene, isoprenylene, 2-butenylene, and 2-hexenylene. An alkenylene group can be optionally substituted with one or more substituents such as alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, amino, nitro, carboxy, cyano, halo, hydroxy, sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino, heterocycloalkylcarbonylamino, heterocycloalkylalkylcarbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, urea, thiourea, sulfamoyl, sulfamide, alkoxycarbonyl, or alkylcarbonyloxy. 
     As used herein, the term “alkynylene” group refers to an aliphatic carbon group that contains 2-10 (e.g., 2-6 or 2-4) carbon atoms and has at least one triple bond. An alkynylene group can be straight or branched. Examples of an alkynylene group include, but are not limited to, propargylene and butynylene. An alkynylene group can be optionally substituted with one or more substituents such as alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, amino, nitro, carboxy, cyano, halo, hydroxy, sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino, heterocycloalkylcarbonylamino, heterocycloalkylalkylcarbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, urea, thiourea, sulfamoyl, sulfamide, alkoxycarbonyl, or alkylcarbonyloxy. 
     As used herein, the term “cycloalkyl” group refers to an aliphatic carbocyclic ring of 3-10 (e.g., 4-8) carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantly, norbornyl, cubyl, octahydroindenyl, decahydronaphthyl; bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, and bicyclo[3.2.3]nonyl. 
     As used herein, the term “alkoxy” group refers to an alkyl-O-group where “alkyl” has been defined previously. 
     As used herein, the term “haloalkyl” group refers to an alkyl group containing one or more halogen atoms. Examples of haloalkyl groups include fluoromethyl, chloromethyl, bromomethyl, and trifluoromethyl. 
     As used herein, the term “halogen” or “halo” group refers to fluorine, chlorine, bromine or iodine. 
     As used herein, the term “ALK5 and/or ALK4 inhibitor” refers to a compound, other than inhibitory Smads, e.g. Smad6 and Smad7, which selectively inhibits the ALK5 and/or ALK4 receptors preferentially over p38 or type II receptors. 
     As used herein, the term “ALK5- and/or ALK4-mediated disease state” refers to any disease state which is mediated (or modulated) by ALK5 and/or ALK4, for example, a disease which is modulated by the inhibition of the phosphorylation of Smad2 and Smad3 in the TGF-β and/or activin signaling pathways. 
     As used herein, the term “ulcers” is used to include, but not to be limited to, diabetic ulcers, chronic ulcers, gastric ulcers, and duodenal ulcers. 
     Compounds of formula (I) may be prepared by a number of known methods from commercially available or known starting materials. If the starting materials are unavailable from a commercial source, they can be prepared by procedures known in the art. 
     
       
                 
         
             
             
         
      
     
     In one method, compounds of formula (I) wherein A 1  is N and A 2  is NH, or A 1  is NH and A 2  is N are prepared according to Scheme 1. Specifically, optionally substituted 2-methylpyridine (II) is deprotonated by a base such as n-BuLi, NaHMDS, LDA or LiHMDS before reacting with R 1 COOR 8  (III) wherein R 8  is C 1-6 alkyl, R 1 COCl (IV), or R 1 -substituted carboxylic acid methoxy-methyl-amide (V) to form a ketone (VI). The methoxy-methyl-amide (V) can be prepared by reacting a corresponding acid chloride (IV) with N,O-dimethylhydroxylamine hydrochloride. The ketone (VI) may be oxidized to a diketone (VII) with HBr in DMSO. This diketone (VII) can then be condensed with an appropriately substituted aldehyde (VIII) or protected aldehyde derivative in the presence of ammonium acetate to yield a compound of formula (I). R 1 , R 2 , R 3 , and X have been defined as above. The aldehyde (VIII) can be prepared according to the methods outlined in WO 02/096875 A1 and  Liquid Crystals  10:273-287 (1991). Alternatively, the ketone (VI) can be treated with sodium nitrite in HCl or acetic acid to afford an (x-keto-oxime (IX), which can be then condensed with an appropriately substituted aldehyde (VIII) or protected aldehyde derivative in the presence of ammonium acetate to give the N-hydroxyimidazoles. Treatment of this with triethylphophite affords a compound of formula (I). 
     The resulting compounds of this invention represented by the formula (I)-(IX) can be separated and purified by appropriate conventional methods such as column chromatography and recrystallization. 
     Compounds of the invention may be administered by any suitable route, for example by oral, buccal, sub-lingual, rectal, vaginal, nasal, topical or parenteral (including intravenous, intramuscular, subcutaneous and intracoronary) administration. 
     The topical formulations of the present invention may be presented as, for instance, ointments, creams or lotions, eye ointments and eye or ear drops, impregnated dressings and aerosols, and may contain appropriate conventional additives such as preservatives, solvents to assist drug penetration and emollients in ointments and creams. 
     The formulations may also contain compatible conventional carriers, such as cream or ointment bases and ethanol or oleyl alcohol for lotions. Such carriers may be present as from about 1% up to about 98% of the formulation. More usually, they will form up to about 80% of the formulation. 
     For administration to man in the curative or prophylactic treatment of the disorders identified above, oral, buccal or sub-lingual dosages of a compound of formula (I) will generally be in the range of from 50-5000 mg daily for an average adult patient (70 kg). Thus for a typical adult patient, individual tablets or capsules contain from 25-500 mg of active compound, in a suitable pharmaceutically acceptable vehicle or carrier, for administration in single or multiple doses, once or several times per day. Dosages for parenteral administration will typically be within the range of from 25-250 mg per single dose as required. In practice the physician will determine the actual dosing regimen which will be most suitable for an individual patient and it will vary with the age, weight and response of the particular patient. The above dosages are exemplary of the average case but there can be individual instances in which higher or lower dosage ranges may be merited, and such are within the scope of this invention. 
     For human use, a compound of formula (I) can be administered alone, but will generally be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice. For example, the compound may be administered orally, buccally or sublingually, in the form of tablets containing excipients such as starch or lactose, or in capsules or ovules either alone or in admixture with excipients, or in the form of elixirs or suspensions containing flavoring or coloring agents. Such liquid preparations may be prepared with pharmaceutically acceptable additives such as suspending agent (e.g. methylcellulose, a semi-synthetic glyceride such as witepsol or mixtures of glycerides such as a mixture of apricot kernel oil and PEG-6 esters or mixtures of PEG-8 and caprylic/capric glycerides). A compound may also be injected parenterally, for example intravenously, intramuscularly, subcutaneously or intracoronarily. For parenteral administration, the compound is best used in the form of a sterile aqueous solution which may contain other substances, for example, salts, or monosaccharides such as mannitol or glucose, to make the solution isotonic with blood. 
     Thus, the invention provides in a further aspect a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable diluent or carrier therefor. 
     The invention also provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition containing either entity, for use in therapy. 
     The invention further provides the use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the treatment of a disease, mediated by the ALK5 and/or ALK4 receptors in mammals. 
     ALK5- and/or ALK4-mediated disease states include, but are not limited to, glomerulonephritis, diabetic nephropathy, lupus nephritis, hypertension-induced nephropathy, renal interstitial fibrosis, renal fibrosis resulting from complications of drug exposure, HIV-associated nephropathy, transplant necropathy, liver fibrosis due to all etiologies, hepatic dysfunction attributable to infections, alcohol-induced hepatitis, disorders of the biliary tree, pulmonary fibrosis, acute lung injury, adult respiratory distress syndrome, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, pulmonary fibrosis due to infectious or toxic agents, post-infarction cardiac fibrosis, congestive heart failure, dilated cardiomyopathy, myocarditis, vascular stenosis, restenosis, atherosclerosis, ocular scarring, corneal scarring, proliferative vitreoretinopathy, excessive or hypertrophic scar or keloid formation in the dermis occurring during wound healing resulting from trauma or surgical wounds, peritoneal and sub-dermal adhesion, scleroderma, fibrosclerosis, progressive systemic sclerosis, dermatomyositis, polymyositis, arthritis, osteoporosis, ulcers, impaired neurological function, male erectile dysfunction, Peyronie&#39;s disease, Dupuytren&#39;s contracture, Alzheimer&#39;s disease, Raynaud&#39;s syndrome, fibrotic cancers, tumor metastasis growth, radiation-induced fibrosis, and thrombosis. 
     The invention further provides a method of inhibiting the TGF-β and/or activin signaling pathways in mammals, for example, inhibiting the phosphorylation of Smad2 or Smad3 by ALK5 and/or ALK4. 
     The invention further provides a method of reducing the accumulation of excess extracellular matrix in mammals by inhibiting the TGF-β and/or activin signaling pathways, for example, inhibiting the phosphorylation of Smad2 or Smad3 by ALK5 and/or ALK4. 
     The invention further provides a method of inhibiting metastasis of tumor cells in mammals by inhibiting the TGF-β signaling pathway. 
     The invention further provides a method of treating carcinomas mediated by an overexpression of TGF-β in mammals by inhibiting the TGF-β signaling pathway. 
     The present invention is further illustrated in the following Examples, which should not be taken to limit the scope of the invention described in the claims. In the Examples, electrospray ionization mass spectra (ESI-MS) were obtained on a LCQ DECA XP Plus mass spectrometer (Thermo Finnigan, USA). 
     EXAMPLES 
     Practice Example 1 
     Preparation of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide (Example 79) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile (Example 78, prepared according to the method described in US 2008/0319012 A1) (130 mg, 0.31 mmol) in acetic acid (3 mL) was added conc. H 2 SO 4  (0.7 mL) and the mixture was stirred at 100° C. After 2 hours, more conc. H 2 SO 4  (0.2 mL) was added and the mixture was stirred at 100° C. for 1 hour. Then the reaction mixture was cooled to room temperature, diluted with H 2 O (10 mL) in the ice bath, and neutralized by addition of NH 4 OH solution to pH 7. The mixture was extracted with CH 2 Cl 2  (3 times) and then the organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:20 (v/v) to 1:10 (v/v)) to afford the solid, which was recrystallized from CH 2 Cl 2 /MeOH/Et 2 O to give the title compound (131.6 mg, 68%).  1 H NMR (300 MHz, CD 3 OD) δ 2.53 (3H, s), 4.23 (2H, s), 7.16-7.23 (3H, m), 7.54-7.59 (2H, m), 7.84 (1H, dd), 8.04 (2H, bs), 8.25 (1H, bs), 8.85 (2H, dd). MS (ESI) m/z 439 (MH + ). 
     Practice Example 2 
     Preparation of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol (Example 81) 
     
       
                 
         
             
             
         
      
     
     A mixture of 6-(2-(4-fluoro-3-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 80, prepared according to the method described in US 2008/0319012 A1) (948 mg, 2.23 mmol) and pyridine hydrochloride (95 g) was stirred at 190° C. for 80 min. Then the hot reaction mixture was poured into H 2 O (60 mL) and added NH 4 OH solution to pH 5. The aqueous solution was extracted with CH 2 Cl 2  (30 mL, 7 times) and then the organic layer was dried over MgSO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:30 (v/v) to 1:15 (v/v)) to afford the solid, which was recrystallized from CH 2 Cl 2 /Et 2 O to give the title compound (635 mg, 69%).  1 H NMR (300 MHz, CDCl 3 ) δ 2.34 (3H, s), 3.95 (2H, s), 6.50 (1H, d), 6.56-6.57 (1H, m), 6.79 (1H, dd), 6.91 (1H, d), 7.25-7.33 (2H, m), 7.78 (1H, m), 7.91-7.97 (2H, m), 8.03 (1H, s), 8.81 (1H, d), 10.80 (1H, bs), 11.48 (1H, bs). MS (ESI) m/z 411 (MH + ). 
     Practice Example 3 
     Preparation of 6-(2-(4-fluoro-3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 87) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol (Example 81) (80 mg, 0.195 mmol) in acetone (6 mL) and DMF (3 mL) were added 1-(2-chloroethyl)pyrrolidine hydrochloride (50 mg, 0.292 mmol) and K 2 CO 3  (81 mg, 0.585 mmol). The mixture was stirred at 60° C. for 6 hours, cooled to room temperature, and diluted with H 2 O (10 mL). The mixture was extracted with CH 2 Cl 2  (25 mL, 3 times), and then the organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH 2 Cl 2 =1:50 (v/v) to 1:20 (v/v)) to afford the title compound (52.7 mg, 53%).  1 H NMR (300 MHz, CDCl 3 ) δ 1.78 (4H, pentet), 2.51 (3H, s), 2.63 (4, td), 2.93 (2H, t), 4.16 (2H, s), 7.18 (2H, t), 6.85-6.90 (1H, m), 6.94-7.07 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.41 (1H, dd), 7.97 (1H, dd), 8.09-8.18 (3H, m), 8.92 (1H, dd), 10.01 (1H, bs). MS (ESI) m/z 508 (MH + ). 
     Practice Example 4 
     Preparation of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (Example 73) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 72, prepared according to the method described in US 2008/0319012 A1) (448 mg, 1.02 mmol) in MeOH (30 mL) were added ammonium formate (257 mg, 4.08 mmol) and 10% Pd/C (30 mg) and the mixture was stirred at room temperature for 100 min. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was diluted with H 2 O (50 mL) and added 2N HCl solution until all remaining substances were dissolved. The aqueous solution was neutralized by addition of NH 4 OH solution to pH 7. The precipitate was filtered, washed with H 2 O, and dried under vacuum. The precipitate was purified by MPLC (MeOH:CH 2 Cl 2 =1:20 (v/v) to 1:15 (v/v)) to afford the title compound (445.5 mg, 80%).  1 H NMR (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.10 (2H, s), 6.64-6.72 (2H, m), 6.92 (1H, d), 6.95 (1H, d), 7.24 (1H, s), 7.35-7.39 (1H, m), 7.41 (1H, dd), 7.96 (1H, dd), 8.10 (1H, d), 8.14-8.17 (2H, m), 8.91 (1H, dd). MS (ESI) m/z 410 (MH + ). 
     Practice Example 5 
     Preparation of 2-chloro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (Example 75) 
     
       
                 
         
             
             
         
      
     
     To a suspension of 6-(2-(4-chloro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 74, prepared according to the method described in US 2008/0319012 A1) (50 mg, 0.110 mmol) in MeOH (2 mL) was added SnCl 2  (104 mg, 0.548 mmol) and the mixture was stirred at 55° C. After 2.5 hours, the reaction mixture was cooled to room temperature, concentrated under reduced pressure. The residue was diluted with H 2 O (5 mL), filtered, and the filtrate was washed with 2N HCl (5 mL) and neutralized by addition of 5N NaOH solution to pH 7˜8. The precipitate was filtered, washed with H 2 O and Et 2 O, and dried under vacuum for overnight. The precipitate was purified by MPLC on silica gel (MeOH:EA:CH 2 Cl 2 =1:20:80 (v/v) to 1:4:16 (v/v)), and on NH silica gel (MC) to afford the title compound (33.1 mg, 71%).  1 H NMR (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.09 (2H, s), 6.66 (1H, dd), 6.68 (1H, s), 6.96 (1H, d), 7.19 (1H, d), 7.25 (1H, bs), 7.36-7.39 (1H, m), 7.40 (1H, dd), 7.96 (1H, d), 8.10 (1H, d), 8.15-8.16 (2H, m), 8.91 (1H, dd). MS (ESI) m/z 426 (MH + ). 
     Practice Example 6 
     Preparation of 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenylamino)ethanol (Example 90) 
     
       
                 
         
             
             
         
      
     
     To a suspension of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (Example 73) (100 mg, 0.244 mmol) in toluene (450 uL) and DMF (0.2 mL) were added 2-bromoethanol (21 uL, 0.293 mmol), N,N-diisopropylethylamine (300 uL, 1.72 mmol) and the mixture was stirred at 70° C. After 5 hours, additional 2-bromoethanol (5 uL) was added, and stirred at 100° C. for overnight. The reaction mixture was cooled to room temperature, diluted with H 2 O (4 mL), and extracted with CH 2 Cl 2  (2 mL, 3 times). The organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH 2 Cl 2 =1:50 (v/v)) to afford the title compound (38 mg, 34%).  1 H NMR (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 3.31 (2H, bs), 3.83 (2H, t), 4.10 (2H, s), 6.56-6.60 (1H, m), 6.76 (1H, d), 6.87-6.96 (2H, m), 7.22 (1H, d), 7.34-7.42 (2H, m), 7.93 (1H, d), 8.09 (1H, d), 8.15 (2H, bs), 8.90 (1H, dd), 10.45 (1H, bs). MS (ESI) m/z 454 (MH + ). 
     Practice Example 7 
     Preparation of 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanamine (Example 96) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol (Example 81) (100 mg, 0.244 mmol) in acetone (5 mL) were added tert-butyl 2-bromoethylcarbamate (109 mg, 0.488 mmol) and K 2 CO 3  (67 mg, 0.488 mmol) and the mixture was stirred at 60° C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with H 2 O (20 mL), and extracted with CH 2 Cl 2  (5 mL, 3 times). The organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH 2 Cl 2 =1:50 (v/v)) to give tert-butyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethylcarbamate (123.5 mg, 91%). This compound was dissolved in CH 2 Cl 2  (5 mL), and p-anisole (224 uL, 2.23 mmol) and trifluoroacetic acid (1 mL) were added. The mixture was stirred for 1 hour, then concentrated, diluted with H 2 O (10 mL), and neutralized by addition of aqueous NH 4 OH solution to pH 7˜8. The aqueous solution was saturated with NH 4 Cl solid, extracted with CH 2 Cl 2  (5 mL, 3 times), and then the organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH 2 Cl 2 =3:100 (v/v)) to afford the title compound (70.2 mg, 69%).  1 H NMR (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.09 (2H, t), 4.04 (2H, t), 4.16 (2H, s), 6.85-6.90 (1H, m), 6.95-7.07 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.41 (1H, dd), 7.97 (1H, dd), 8.09-8.18 (3H, m), 8.92 (1H, dd), 10.40 (1H, bs). MS (ESI) m/z 454 (MH + ). 
     Practice Example 8 
     Preparation of methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate (Example 93) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol (Example 81) (100 mg, 0.244 mmol) in acetone (5 mL) were added methyl 3-chloropropanoate (32 uL, 0.366 mmol) and K 2 CO 3  (67 mg, 0.488 mmol) and the mixture was stirred at 60° C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with H 2 O (20 mL), and extracted with CH 2 Cl 2  (5 mL, 3 times). The organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH 2 Cl 2 =1:50 (v/v)) to afford the title compound (88.4 mg, 75%). (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.74 (3H, s), 4.16 (2H, s), 4.71 (2H, s), 6.91-6.97 (3H, m), 7.06 (1H, td), 7.24 (1H, s), 7.37 (1H, d), 7.42 (1H, dd), 7.97 (1H, d), 8.10-8.18 (3H, m), 8.92 (1H, dd), 10.35 (1H, bs). MS (ESI) m/z 483 (MH + ). 
     Practice Example 9 
     Preparation of 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetamide (Example 97) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate (Example 93) (32.5 mg, 0.067 mmol) was treated with aqueous NH 4 OH (28-30%, 1 mL). The suspension was stirred at room temperature. After 2 hours, the reaction mixture was diluted with H 2 O (3 mL) and stirred for 30 min. The precipitate was filtered, washed with water, and dried under vacuum for overnight to afford the title compound (26.8 mg, 86%). (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.15 (2H, s), 4.51 (2H, s), 5.80 (N—H, 1H, bs), 6.71 (N—H, 1H, bs), 6.63-7.06 (4H, m), 7.25-7.28 (1H, m), 7.37-7.44 (2H, m), 7.94 (1H, dd), 8.10 (1H, d), 8.16-8.18 (2H, m), 8.91 (1H, dd), 11.00 (1H, bs). MS (ESI) m/z 468 (MH + ). 
     Practice Example 10 
     Preparation of 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetic acid (Example 98) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate (Example 93) (47.5 mg, 0.098 mmol) was added aqueous NaOH solution (6 mg, 0.148 mmol, H 2 O (0.3 mL)). The reaction mixture was stirred for 1 hour, then diluted H 2 O (3 mL), and neutralized by addition of acetic acid to pH 7. The precipitate was filtered, washed with water, and dried under vacuum for overnight to afford the title compound (42.6 mg, 93%). (300 MHz, CDCl 3 +CD 3 OD) δ 2.57 (3H, s), 4.04 (N—H, 1H, bs), 4.75 (N—H, 1H, bs), 6.86 (1H, bs), 7.11 (2H, d), 7.23 (1H, d), 7.46-7.53 (2H, m), 7.85 (1H, dd), 8.05 (1H, d), 8.20 (1H, bs), 8.25 (1H, d), 8.87 (1H, dd). MS (EST) m/z 469 (MH + ). 
     Practice Example 11 
     Preparation of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzoic acid (Example 104) 
     
       
                 
         
             
             
         
      
     
     2-Fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile (Example 76) (300 mg, 0.715 mmol) was treated with conc. H 2 SO 4  (2.4 mL) and H 2 O (0.8 ml) and the mixture was stirred at 120° C. for 10 hours. The reaction mixture was cooled to room temperature and basified to pH 9-10 with 5N NaOH solution in the ice bath. The solution was extracted with CH 2 Cl 2  (5 mL, 3 times), and then the aqueous layer was acidified to pH 4 with 2N HCl solution. The precipitate was filtered, washed with H 2 O, and dried under vacuum for overnight to afford the title compound (213 mg, 49%). (300 MHz, CDCl 3 +CD 3 OD) δ 2.48 (3H, s), 4.15 (2H, s), 6.97 (1H, d), 7.05 (1H, dd), 7.14 (1H, d), 7.35-7.42 (2H, m), 7.47-7.52 (1H, m), 7.83 (1H, dd), 7.90 (1H, dd), 8.01 (1H, d), 8.08 (1H, d), 8.16 (1H, dd), 8.80 (1H, dd). MS (ESI) m/z 439 (MH + ). 
     Practice Example 12 
     Preparation of 6-(2-(4-fluoro-3-(1H-tetrazol-5-yl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 105) 
     
       
                 
         
             
             
         
      
     
     A mixture of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile (Example 76) (100 mg, 0.238 mmol) and sodium azide (20.9 mg, 0.321 mmol) in toluene (1 mL) was stirred at 120° C. for overnight. The reaction mixture was cooled to room temperature and basified to pH 9-10 with 5N NaOH solution in the ice bath. The mixture was extracted with CH 2 Cl 2  (5 mL, 3 times), and then the aqueous layer was acidified to pH 4 with 2N HCl solution. The precipitate was filtered, washed with H 2 O, and dried under vacuum for overnight to afford the solid, which was recrystallized from MeOH/CH 2 Cl 2 /Et 2 O to give the title compound (56 mg, 51%). (300 MHz, CDCl 3 +CD 3 OD) δ 2.49 (3H, s), 4.17 (2H, s), 6.98 (1H, d), 7.08 (1H, dd), 7.13 (1H, d), 7.35-7.41 (2H, m), 7.45-7.50 (1H, m), 7.81 (1H, dd), 7.97-8.01 (2H, m), 8.05 (1H, d), 8.13 (1H, dd), 8.80 (1H, dd). MS (ESI) m/z 463 (MH + ). 
     Practice Example 13 
     Preparation of 2-fluoro-N-(2-hydroxyethyl)-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide (Example 107) 
     
       
                 
         
             
             
         
      
     
     A mixture of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzoic acid (Example 104) (50 mg, 0.114 mmol), HOBt (23 mg, 0.171 mmol), DMAP (3 mg, 0.023 mmol), and 2-aminoethanol in pyridine (1 mL) was added EDC (33 mg, 0.171 mmol) and the mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into H 2 O and extracted with CH 2 Cl 2  (5 mL, 3 times). The organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:100 (v/v) to 1:20 (v/v)) to afford the title compound (34.7 mg, 61%). (300 MHz, CDCl 3 ) δ 2.37 (3H, s), 3.57 (2H, q), 3.79 (2H, t), 4.15 (2H, s), 6.91 (1H, dd), 6.96 (1H, d), 7.04-7.15 (1H, m), 7.20-7.30 (1H, m), 7.37-7.43 (2H, m), 7.80 (1H, dd), 7.85 (1H, dd), 8.04 (1H, d), 8.10 (1H, d), 8.14 (1H, dd), 8.90 (1H, dd), MS (ESI) m/z 482 (MH + ). 
     Practice Example 14 
     Preparation of (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanamine (Example 108) 
     
       
                 
         
             
             
         
      
     
     To a suspension of 2-Fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile (Example 76) (100 mg, 0.238 mmol) in THF (1.5 mL) was added LAH (1M solution in THF, 476 uL, 0.476 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction was quenched by addition of ethyl acetate (1 mL) and H 2 O (3 drops), and the mixture was stirred for 30 min. The mixture was dried over Na 2 SO 4 , filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:50 (v/v) to 1:20 (v/v)) to afford the title compound (53.2 mg, 53%). (300 MHz, CDCl 3 +CD 3 OD) δ 2.49 (3H, s), 3.87 (2H, s), 4.17 (2H, s), 6.95-7.01 (2H, m), 7.17-7.33 (3H, m), 7.35-7.43 (2H, m), 7.96 (1H, d), 8.08-8.17 (3H, m), 8.91 (1H, dd), 10.40 (1H, bs), MS (ESI) m/z 424 (MH + ). 
     Practice Example 15 
     Preparation of (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanol (Example 109) 
     
       
                 
         
             
             
         
      
     
     To a suspension of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzoic acid (Example 104) (75 mg, 0.171 mmol) in THF (1 mL) was added LAH (1M solution in THF, 342 uL, 0.342 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction was quenched by addition of ethyl acetate (1 mL) and H 2 O (3 drops), and the mixture was stirred for 30 min. The mixture was dried over Na 2 SO 4 , filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:50 (v/v) to 1:20 (v/v)) to afford the title compound (16.9 mg, 23%). (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.09 (2H, s), 6.64-6.72 (2H, m), 6.91-6.98 (2H, m), 7.31 (1H, d), 7.39 (1H, t), 8.13 (2H, d), 8.41 (1H, s), 8.84 (2H, dd), MS (ESI) m/z 411 (MH + ). 
     Practice Example 16 
     Preparation of 6-(5-(6-methylpyridin-2-yl)-2-(3-(pyrrolidin-1-yl)benzyl)-1H-imidazol-4-yl)quinoline (Example 110) 
     
       
                 
         
             
             
         
      
     
     To a solution of 6-(5-(6-methylpyridin-2-yl)-2-(3-nitrobenzyl)-1H-imidazol-4-yl)quinoline (500 mg, 1.186 mmol, prepared according to the method described in US 2008/0319012 A1) in MeOH (5 mL) was added Pd/C (0.5 mg, 10% w/w) and the mixture was stirred under H 2  at atmospheric pressure for 5 hours. The reaction mixture was filtered through celite and the filterate was concentrated under reduced pressure. The residue was purified by MPLC on silica gel (MeOH:CH 2 Cl 2 =1:50) to afford the 3-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (424 mg, 91%). The obtained compound, 3-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (30 mg, 0.077 mmol) was dissolved in DMF (3 mL), treated with 1,4-dibromobutane (17 mg, 0.080 mmol), and stirred at 120° C. for 12 hours. The reaction mixture was cooled to room temperature, added H 2 O (30 mL), and extracted with ethyl acetate. The organic layer was dried over Na 2 SO 4 , filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:20 (v/v)) and on NH silica gel (MeOH:CH 2 Cl 2 =1:100 (v/v)) to afford the title compound (7 mg, 20.5%). (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.09 (2H, s), 6.64-6.72 (2H, m), 6.91-6.98 (2H, m), 7.31 (1H, d), 7.39 (1H, t), 8.13 (2H, d), 8.41 (1H, s), 8.84 (2H, dd), MS (ESI) m/z 411 (MH + ). 
     Practice Example 17 
     Preparation of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)aniline (Example 112) 
     
       
                 
         
             
             
         
      
     
     To a stirred solution of 6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline (49.6 mg, 0.113 mmol, prepared according to the method described in US 2008/0319012 A1) in MeOH (5 mL) were added Raney Ni (0.1 mg, 10% w/w) and hydrazine monohydrate (0.027 mL, 0.563 mmol) and the mixture was stirred at room temperature for overnight. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by MPLC (MeOH:CH 2 Cl 2 =1:50 (v/v)) and on NH silica gel (MeOH:CH 2 Cl 2 =1:100 (v/v)) to afford the title compound (37.8 mg, 82%). (300 MHz, CDCl 3 ) δ 1.99 (4H, m), 2.54 (3H, s), 3.23 (4H, t), 4.31 (2H, s), 6.37 (1H, dd), 6364 (1H, d), 6.95 (1H, d), 7.23-7.43 (5H, m), 7.98 (1H, dd), 8.08-8.17 (3H, m), 8.91 (1H, dd), 10.40 (1H, bs) MS (ESI) m/z 446 (MH + ). 
     The compounds listed in the following Table 1 were prepared in an analogous manner to those described in US 2008/0319012 A1 and the Practice Examples 1-17 above. The  1 H NMR and mass spectral data of these compounds are included in the Table 1. 
                                                   TABLE 1                           Mass                   data                   (m/z)       Example   Structure     1 H NMR   (MH + )                                1                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.27 (2H, s), 6.96 (1H, d), 7.29 (1H, bs), 7.36-7.47 (3H, m), 7.52 (1H, s), 7.54 (1H, s), 7.63 (1H, s), 7.97 (1H, dd), 8.11 (1H, d), 8.10-8.18 (3H, m), 8.92 (1H, dd)   445               2                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.20 (2H, s), 6.91-6.96 (2H, m), 7.05 (1H, dd), 7.10 (1H, d), 7.24-7.32 (2H, m), 7.37 (1H, d), 7.41 (1H, dt), 7.97 (1H, dd), 7.97 (1H, dd), 8.10-8.19 (3H, m), 8.92 (1H, dd)   395               3                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.18 (2H, s), 6.96 (1H, d), 7.20 (1H, d), 7.28 (2H, bs), 7.37-7.43 (3H, m), 7.50 (1H, bs), 7.97 (1H, dd), 8.10-8.18 (3H, m), 8.92 (1H, dd)   456               4                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.19 (2H, s), 6.96 (1H, d), 7.20-7.28 (4H, m), 7.34 (1H, bs), 7.39 (1H, d), 7.42 (1H, t), 7.98 (1H, dd), 8.10-8.19 (3H, m), 8.92 (1H, dd)   411               5                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.06 (3H, s), 4.30 (2H, s), 6.97 (1H, d), 7.29 (1H, s), 7.37-7.44 (2H, m), 7.53 (1H, t), 7.65 (1H, d), 7.84 (1H, dt), 7.95 (1H, bs), 7.98 (1H, d), 8.10-8.18 (3H, m), 8.92 (1H, dd)   455               6                                 (300 MHz, CDCl 3 ) δ 4.28 (2H, s), 7.28 (1H, bs), 7.36 (1H, t), 7.44 (1H, dd), 7.46 (1H, d), 7.49 (1H, s), 7.54-7.56 (2H, m), 7.63 (1H, s), 7.92 (1H, dd), 8.12-8.19 (3H, m), 8.93 (1H, dd)   510               7                                 (300 MHz, CDCl 3 ) δ 4.22 (2H, s), 6.98 (1H, td), 7.07 (1H, dt), 7.12 (1H, d), 7.25- 7.28 (1H, m), 7.31 (2H, dd), 7.41 (1H, d), 7.43 (1H, d), 7.93 (1H, dd), 8.12-8.19 (3H, m), 8.93 (1H, dd)   460               8                                 (300 MHz, CDCl 3 ) δ 4.15 (2H, s), 7.19 (1H, t), 7.24 (1H, td), 7.25-7.32 (3H, m), 7.31 (2H, dd), 7.34 (1H, s), 7.37 (1H, td), 7.43 (1H, dd), 7.50 (1H, t), 7.87 (1H, dd), 8.08 (1H, dd), 8.14 (1H, d), 8.21 (1H, dd), 8.86 (1H, dd)   521               9                                 (300 MHz, CDCl 3 ) δ 4.21 (2H, s), 7.23- 7.30 (4H, m), 7.34 (2H, td), 7.41 (1H, bs), 7.45 (1H, dd), 7.93 (1H, dd), 8.13-8.21 (3H, m), 8.94 (1H, dd)   476               10                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 2.77 (3H, s), 4.27 (2H, s), 6.95 (1H, d), 7.29-7.37 (3H, m), 7.46 (1H, d), 7.53 (2H, bs), 7.63 (1H, s), 7.92 (1H, dd), 8.01-8.07 (2H, m), 8.11 (1H, s)   459               11                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 2.77 (3H, s), 4.18 (2H, s), 6.94 (1H, d), 7.20 (1H, t), 7.24-7.31 (3H, m), 7.35 (1H, d), 7.40 (1H, td), 7.51 (1H, bs), 7.92 (1H, dd), 8.04 (2H, dt), 8.12 (1H, d)   470               12                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 2.77 (3H, s), 4.18 (2H, s), 6.94 (1H, d), 7.21-7.39 (7H, m), 7.93 (1H, dd), 8.04 (2H, dt), 8.12 (1H, d)   425               13                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 2.77 (3H, s), 4.21 (2H, s), 6.93-6.99 (2H, m), 7.06 (1H, dt), 7.15 (1H, dt), 7.24-7.29 (2H, m), 7.31 (1H, s), 7.35 (1H, d), 7.92 (1H, dd), 8.05 (2H, t), 8.12 (1H, d)   409               14                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 5.77 (3H, s), 3.07 (3H, s), 4.31 (2H, s), 6.96 (1H, d), 7.25-7.32 (2H, m), 7.37 (1H, t), 7.55 (1H, t), 7.68 (1H, dt), 7.85 (1H, dt), 7.92 (1H, dd), 7.96 (1H, bs), 8.01-8.07 (2H, m), 8.10 (1H, m)   469               15                                 (300 MHz, CDCl 3 ) δ 2.77 (3H, s), 4.28 (2H, s), 7.24 (1H, d), 7.27-7.34 (1H, m), 7.39 (1H, bs), 7.48 (1H, dt), 7.50 (1H, d), 7.54 (2H, bs), 7.56 (1H, d), 7.64 (1H, s), 7.88 (1H, dd), 8.04 (1H, d), 8.08 (1H, d), 8.11 (1H, s)   524               16                                 (300 MHz, CDCl 3 ) δ 2.77 (3H, s), 4.18 (2H, s), 7.19-7.33 (5H, m), 7.41 (2H, td), 7.50 (1H, s), 7.88 (1H, dd), 8.03-8.07 (2H, m), 8.10 (1H, s)   535               17                                 (300 MHz, CDCl 3 ) δ 2.70 (3H, s), 4.10 (2H, s), 7.19-7.23 (4H, m), 7.27 (1H, s), 7.29- 7.31 (3H, m), 7.79 (1H, dd), 7.96 (1H, d), 8.04-8.05 (1H, m), 8.07 (1H, s)   490               18                                 (300 MHz, CDCl 3 ) δ 2.77 (3H, s), 4.21 (2H, s), 6.98 (1H, td), 7.07 (1H, dt), 7.13 (1H, d), 7.24 (1H, d), 7.26-7.37 (4H, m), 7.88 (1H, dd), 8.03 (1H, d), 8.06 (1H, d), 8.10 (1H, s)   474               19                                 (300 MHz, CDCl 3 ) δ 2.57 (3H, s), 3.90 (3H, s), 6.93-7.00 (3H, m), 7.33 (1H, bs), 7.39- 7.45 (2H, m), 7.55-7.65 (5H, m)   424               20                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 3.88 (3H, s), 4.16 (2H, s), 6.92-6.99 (3H, m), 7.22- 7.28 (3H, m), 7.33 (2H, d), 7.39 (1H, d), 7.59 (2H, dt)   390               21                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.22 (2H, s), 6.95 (1H, d), 7.23 (1H, s), 7.36-7.44 (4H, m), 7.48-7.52 (2H, m), 7.57-7.60 (3H, m)   428               22                                 (300 MHz, CDCl 3 ) δ 2.44 (3H, s), 4.14 (2H, s), 6.92-6.97 (2H, m), 7.01 (1H, dt), 7.06 (1H, d), 7.23-7.31 (2H, m), 7.36- 7.43 (3H, m), 7.58 (1H, s), 7.61 (1H, s)   378               23                                 (300 MHz, CDCl 3 ) δ 2.46 (3H, s), 4.21 (2H, s), 6.00 (2H, s), 6.85 (1H, d), 6.92 (1H, s), 7.10 (2H, bs), 7.31 (1H, d), 7.41 (1H, t), 7.42 (1H, t), 7.50-7.52 (2H, m), 7.60 (1H, s)   438               24                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.12 (2H, s), 6.00 (2H, s), 6.86 (1H, d), 6.92 (1H, s), 7.12-7.25 (4H, m), 7.30 (1H, s), 7.33 (1H, s), 7.41 (1H, t)   404               25                                 (300 MHz, CDCl 3 ) δ 2.43 (3H, s), 4.14 (2H, s), 6.00 (2H, s), 6.85 (1H, dd), 6.91 (1H, d), 6.93 (1H, td), 7.01 (1H, dt), 7.06 (1H, d), 7.10 (1H, s), 7.12 (1H, dd), 7.22-7.27 (2H, m), 7.30 (1H, d), 7.40 (1H, t)   388               26                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.26 (2H, s), 6.97 (1H, d), 7.34 (1H, d), 7.42 (2H, m), 7.50 (1H, s), 7.53 (1H, s), 7.62 (1H, s), 8.14 (2H, s), 8.41 (1H, s), 8.84 (2H, dd)   446               27                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.19 (2H, s), 6.98 (1H, d), 7.20-7.25 (3H, m), 7.34- 7.44 (3H, m), 8.13 (1H, s), 8.14 (1H, s), 8.41 (1H, s), 8.84 (1H, d), 8.85 (1H, d)   412               28                                 (300 MHz, CDCl 3 ) δ 2.43 (3H, s), 4.19 (2H, s), 6.91 (1H, dd), 6.96 (1H, d), 7.03 (1H, dt), 7.08 (1H, d), 7.23-7.44 (3H, m), 8.14 (2H, bs), 8.42 (1H, s), 8.84 (2H, dd)   396               29                                 (300 MHz, CDCl 3 ) δ 4.28 (2H, s), 7.12 (1H, dd), 7.37 (1H, bs), 7.42 (1H, d), 7.45 (1H, d), 7.52 (1H, d), 7.55 (1H, s), 7.58 (1H, s), 7.64 (1H, s), 7.93 (1H, dd), 8.13 (1H, s), 8.16 (1H, d), 8.20 (1H, d), 8.94 (1H, dd)   465               30                                 (300 MHz, CDCl 3 ) δ 4.18 (2H, s), 7.09 (1H, dd), 7.23-7.27 (4H, m), 7.33 (1H, bs), 7.40 (1H, d), 7.42 (1H, d) 7.91 (1H, dd), 8.10-8.17 (3H, m), 8.92 (1H, dd)   432               31                                 (300 MHz, CDCl 3 ) δ 2.53 (3H, s), 4.22 (2H, s), 7.01 (1H, d), 7.25-7.32 (4H, m), 7.38 (1H, s), 7.41-7.46 (2H, m), 8.03 (1H, d), 8.05 (1H, s), 8.15 (1H, d), 8.21 (1H, s)   446               32                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.24 (2H, s), 6.94 (1H, d), 7.06-7.13 (2H, m), 7.21- 7.27 (2H, m), 7.34-7.42 (3H, m), 7.96 (1H, dd), 8.08 (1H, s) 8.13 (1H, d), 8.17 (1H, s), 8.91 (1H, dd)   395               33                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.19 (2H, s), 6.98 (1H, d), 7.00-7.05 (2H, m), 7.24- 7.35 (3H, m), 7.38 (1H, s), 7.41 (1H, dd), 7.97 (1H, dd), 8.09 (1H, s), 8.14 (1H, d), 8.18 (1H, s), 8.92 (1H, dd)   395               34                                 (300 MHz, CDCl 3 ) δ 2.56 (3H, s), 4.17 (2H, s), 6.99 (1H, dd), 7.04 (1H, d), 7.20 (1H, bs), 7.27 (1H, dt), 7.43 (1H, bs), 7.47 (1H, dd), 7.89 (1H, dd), 8.06 (1H, d), 8.12 (1H, d), 8.23 (1H, d), 8.85 (1H, dd)   431               35                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.25 (2H, s), 6.97 (1H, d), 7.08-7.15 (2H, m), 7.23- 7.32 (2H, m), 7.37-7.43 (2H, m), 8.12 (2H, s), 8.04 (1H, s), 8.91 (2H, dd), 10.16 (1H, bs)   396               36                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.19 (2H, s), 6.97 (1H, d), 6.99-7.05 (2H, m), 7.29- 7.34 (3H, m), 7.38-7.43 (1H, m), 8.14 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.16 (1H, bs)   396               37                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.17 (2H, s), 6.92-7.00 (2H, m), 7.20-7.29 (1H, m), 7.29-7.34 (1H, m), 7.39-7.44 (1H, m), 8.13 (2H, bs), 8.41 (1H, s), 8.85 (2H, dd)   432               38                                 (300 MHz, CDCl 3 ) δ 2.55 (3H, s), 4.15 (2H, s), 7.03 (1H, d), 7.11-7.16 (2H, m), 7.20- 7.26 (2H, m), 7.42 (1H, d), 7.46 (1H, dd), 7.89 (1H, dd), 8.06 (1H, d), 8.13 (1H, d), 8.22 (1H, dd), 8.85 (1H, dd)   413               39                                 (300 MHz, CDCl 3 ) δ 2.56 (3H, s), 4.15 (2H, s), 7.03 (1H, d), 7.10 (1H, t), 7.19 (1H, bs), 7.30-7.35 (1H, m), 7.39-7.41 (1H, m), 7.46 (1H, dd), 7.60 (1H, dd), 7.90 (1H, dd), 8.06 (1H, d), 8.13 (1H, dd), 8.23 (1H, d), 8.86 (1H, dd)   474               40                                 (300 MHz, CDCl 3 ) δ 2.51 (3H, s), 4.42 (2H, s), 6.95 (1H, d), 7.25-7.27 (1H, m), 7.35- 7.39 (2H, m), 7.42 (1H, dd), 7.48-7.55 (2H, m), 7.71 (1H, d), 7.97 (1H, dd), 8.11 (1H, d), 8.16-8.17 (2H, m), 8.92 (1H, m)   445               41                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.26 (2H, s), 6.96 (1H, d), 7.28 (1H, s), 7.36-7.42 (2H, m), 7.44 (1H, s), 7.46 (1H, s), 7.56 (1H, s), 7.59 (1H, s), 7.97 (1H, dd), 8.10 (s, 1H), 8.14 (1H, d), 8.18 (1H, s), 8.92 (1H, dd)   445               42                                 (300 MHz, CDCl 3 ) δ 2.56 (3H, s), 4.32 (2H, s), 7.04 (1H, d), 7.21 (1H, bs), 7.41-7.48 (2H, m), 7.79 (H, s), 7.88-7.90 (1H, m), 7.92 (2H, s), 8.06 (1H, d), 8.13 (1H, dd), 8.22 (1H, d), 8.86 (1H, dd)   513               43                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.54 (3H, s), 4.17 (2H, s), 7.02 (1H, d), 7.19 (1H, bs), 7.31-7.34 (4H, m), 7.39-7.42 (1H, m), 7.46 (1H, dd), 7.89 (1H, dd), 8.06 (1H, d), 8.13 (1H, d), 8.22 (1H, d), 8.85 (1H, dd)   411               44                                 (300 MHz, CDCl3) δ 2.47 (3H, s), 4.18 (2H, s), 6.69 (1H, tt), 6.83-6.90 (2H, m), 6.97 (1H, d), 7.29 (1H, s), 7.38-7.44 (2H, m), 7.97 (1H, dd), 8.11-8.19 (3H, m), 8.93 (1H, dd), 10.27 (1H, bs)   413               45                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.26 (2H, s), 6.96 (1H, d), 7.02-7.15 (3H, m), 7.24 (1H, s), 7.37 (1H, d), 7.41 (1H, dd), 7.96 (1H, dd), 8.11 (1H, d), 8.15-8.17 (2H, m), 8.92 (1H, dd), 10.25 (1H, bs)   413               46                                 (300 MHz, CDCl 3 ) δ 2.46 (3H, s), 4.21 (2H, s) 6.98 (1H, d), 7.14 (1H, t), 7.29 (1H, s), 7.38-7.44 (2H, m), 7.49-7.53 (1H, m), 7.59 (1H, dd), 7.96 (1H, dd), 8.12 (1H, d), 8.17 (2H, bs), 8.92 (1H, dd), 10.28 (1H, bs)   463               47                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 3.85 (3H, s), 4.14 (2H, s), 6.87-6.97 (2H, m), 7.02 (1H, d), 7.08 (1H, d), 7.25-7.27 (1H, m), 7.36- 7.43 (2H, m), 7.96 (1H, dd), 8.11 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.22 (1H, bs)   425               48                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 3.85 (3H, s), 4.13 (2H, s), 6.85 (1H, d), 6.96 (1H, d), 7.17 (1H, dd), 7.27 (1H, m), 7.35 (1H, m), 7.44 (2H, m), 7.96 (1H, dd), 8.11 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd)   441               49                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.21 (2H, s), 6.96 (1H, d), 7.16 (1H, s), 7.19 (1H, d), 7.28 (1H, s), 7.35-7.44 (4H, m), 7.96 (1H, dd), 8.11 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.20 (1H, bs)   461               50                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.27 (2H, s), 6.98 (1H, d). 7.03-7.10 (2H, m), 7.13- 7.18 (1H, m), 7.32 (1H, d), 7.41 (1H, t), 8.12 (2H, s), 8.40 (1H, s), 8.84 (2H, dd), 10.23 (1H, bs)   414               51                                 (300 MHz, CDCl 3 ) δ 2.55 (3H, s), 4.16 (2H, s), 7.05 (1H, d), 7.11-7.16 (2H, m), 7.23- 7.27 (2H, m), 7.44 (1H, bs), 8.07 (2H, bs), 8.33 (1H, s), 8.84 (2H, s)   414               52                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.19 (2H, s), 6.70 (1H, tt), 6.85-6.91 (2H, m), 6.99 (1H, d), 7.33-7.36 (1H, m), 7.40-7.45 (1H, d), 8.14 (2H, s), 8.42 (1H, s), 8.85 (2H, dd), 10.23 (1H, bs)   414               53                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.29 (2H, s), 6.99 (1H, d), 7.21 (1H, t), 7.33 (1H, d), 7.42 (1H, t), 7.52 (1H, td), 7.62 (1H, td), 8.11-8.12 (2H, m), 8.40 (1H, d), 8.84 (2H, dd), 10.27 (1H, bs)   464               54                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.22 (2H, s), 6.99 (1H, d), 7.16 (1H, t), 7.34 (1H, d), 7.42 (1H, t), 7.51-7.56 (1H, m), 7.61 (1H, dd), 8.12-8.14 (2H, m), 8.41 (1H, s), 8.85 (2H, dd), 10.22 (1H, bs)   464               55                                 (300 MHz, CDCl 3 ) δ 2.51 (3H, s), 4.42 (2H, s), 6.97 (1H, d), 7.30-7.42 (3H, m), 7.49- 7.57 (2H, m), 7.71 (1H, d), 8.13 (2H, s), 8.43 (1H, s), 8.84 (2H, dd), 10.08 (1H, bs)   446               56                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.25 (2H, s), 6.97 (1H, d), 7.32-7.39 (2H, m), 7.44 (2H, d), 7.57 (2H, d), 8.14 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.28 (1H, bs)   446               57                                 (300 MHz, CDCl 3 ) δ 2.53 (3H, s), 4.34 (2H, s), 6.99 (1H, d), 7.33-7.44 (2H, m), 7.81 (1H, s), 7.87 (2H, s), 8.10-8.18 (2H, m), 8.42 (1H, s), 8.85 (2H, dd), 10.08 (1H, bs)   514               58                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.15 (2H, s), 6.98 (1H, d), 7.06 (1H, t), 7.22-7.25 (1H, m), 7.33-7.35 (1H, m), 7.40-7.45 (1H, m), 7.54 (1H, dd), 8.14 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.25 (1H, bs)   475               59                                 (300 MHz, CDCl 3 ) δ 2.46 (3H, s), 3.84 (3H, s), 4.13 (2H, s), 6.89 (1H, t), 6.98-7.03 (2H, m), 7.08 (1H, dd), 7.31-7.34 (1H, m), 7.38- 7.43 (1H, m), 8.14 (2H, s), 8.42 (1H s), 8.84 (2H, dd), 10.24 (1H, bs)   426               60                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.18 (2H, s), 6.97 (1H, d), 7.28-7.33 (4H, m), 7.38- 7.43 (1H, m), 8.14 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.12 (1H, bs)   412               61                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.36 (2H, s), 6.98 (1H, d), 7.16 (1H, t), 7.28-7.33 (2H, m), 7.36-7.43 (2H, m), 8.12 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.28 (1H, bs)   447               62                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.15 (2H, s), 6.99 (1H, d), 7.16 (1H, dd), 7.33- 7.45 (4H, m), 8.14 (2H, s), 8.84 (2H, dd), 10.23 (1H, bs)   447               63                                 (300 MHz, CDCl 3 ) δ 2.51 (3H, s), 4.30 (2H, s), 6.98 (1H, d), 7.21 (1H, dd), 7.26- 7.36 (2H, m), 7.41-7.44 (2H, m), 8.12 (2H, s), 8.39 (1H, s), 8.84 (2H, dd)   447               64                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 3.87 (3H, s), 4.13 (2H, s), 6.88 (1H, d), 6.97 (1H, d), 7.19 (1H, dd), 7.32 (1H, d), 7.37 (1H, d), 7.42 (1H, d), 8.14 (2H, s), 8.42 (1H, s), 8.84 (2H, dd), 10.16 (1H, bs)   442               65                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.21 (2H, s), 6.98 (1H, d), 7.16 (1H, s), 7.19 (qH, d), 7.33-7.42 (4H, m), 8.14 (2H, d), 8.41 (1H, s), 8.84 (2H, dd), 10.20 (1H, bs)   462               66                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 3.86 (3H, s), 4.13 (2H, s), 6.84 (1H, d), 6.97 (1H, d), 7.23 (1H, dd), 7.31-7.33 (1H, m), 7.38- 7.43 (1H, m), 7.54 (1H, d), 8.14 (2H, s), 8.42 (1H, s), 8.84 (2H, dd), 10.20 (1H, bs)   487               67                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.20 (2H, s), 6.92 (1H, dd), 6.97 (1H, d), 7.00- 7.05 (3H, m), 7.08-7.13 (2H, m), 7.29- 7.42 (5H, m), 8.13 (2H, s), 8.41 (1H, s), 8.84 (2H, dd), 10.04 (1H, bs)   470               68                                 (300 MHz, CDCl 3 ) δ 2.47 (3H, s), 4.27 (2H, s), 6.97 (1H, d), 7.18 (1H, t), 7.25-7.28 (1H, m), 7.37-7.44 (2H, m), 7.50 (1H, t), 7.58 (1H, t), 7.95 (1H, dd), 8.09-8.17 (3H, m), 8.92 (1H, dd), 10.83 (1H, bs)   463               69                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.54 (3H, s), 4.30 (2H, s), 7.01 (1H, d), 7.19-7.22 (1H, m), 7.24 (1H, dd), 7.34-7.48 (4H, m), 7.91 (1H, dd), 8.08 (1H, d), 8.13 (1H, d), 8.22 (1H, d), 8.87 (1H, dd)   446               70                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 3.85 (3H, s), 4.13 (2H, s), 6.84 (1H, d), 6.96 (1H, d), 7.23 (1H, dd), 7.24-7.28 (1H, m), 7.36- 7.44 (2H, m), 7.53 (1H, d), 7.98 (1H, dd), 8.11 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.38 (1H, bs)   486               71                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.13 (2H, s), 6.00 (2H, s), 6.84-6.87 (1H, m), 6.91- 7.01 (2H, m), 7.09 (1H, s), 7.11 (1H, dd), 7.14-7.23 (1H, m), 7.31 (1H, d), 7.42 (1H, t)   424               72                                 (300 MHz, CD 3 OD) δ 2.53 (3H, s), 4.08 (2H, s), 6.41 (1H, d), 6.42 (1H, bs), 6.61 (1H, dd), 6.84 (1H, bs), 6.94-6.99 (1H, m), 7.18- 7.28 (3H, m), 7.36 (1H, dd), 7.46 (1H, s), 8.06 (2H, dd)   440               73                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.10 (2H, s), 6.64-6.72 (2H, m), 6.92 (1H, d), 6.95 (1H, d), 7.24 (1H, s), 7.35-7.39 (1H, m), 7.41 (1H, dd), 7.96 (1H, dd), 8.10 (1H, d), 8.14- 8.17 (2H, m), 8.91 (1H, dd)   410               74                                 (300 MHz, CDCl 3 ) δ 2.55 (3H, s), 4.25 (2H, s), 7.01 (1H, d), 7.21 (1H, bs), 7.40 (1H, bs), 7.44 (1H, dd), 7.52 (1H, d), 7.59 (1H, dd), 7.91 (1H, d), 7.93 (1H, d), 8.09 (1H, d), 8.13 (1H, d), 8.20 (1H, d), 8.88 (1H, dd)   456               75                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.09 (2H, s), 6.66 (1H, dd), 6.68 (1H, s), 6.96 (1H, d), 7.19 (1H, d), 7.25 (1H, bs), 7.36-7.39 (1H, m), 7.40 (1H, dd), 7.96 (1H, d), 8.10 (1H, d), 8.15-8.16 (2H, m), 8.91 (1H, dd)   426               76                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.52 (3H, s), 4.16 (2H, s), 6.98 (1H, d), 7.13-7.19 (2H, m), 7.35 (1H, d), 7.41 (1H, dd), 7.60-7.64 (2H, m), 7.86 (1H, dd), 8.04 (1H, d), 8.08 (1H, d), 8.17 (1H, d), 8.83 (1H, dd)   420               77                                 (300 MHz, DMSO-d 6 ) δ 2.51 (3H, s), 4.21 (2H, s), 7.15-7.22 (3H, m), 7.52- 7.59 (3H, m), 7.84 (1H, dd), 7.88 (1H, s), 7.99 (1H, s), 8.12 (1H, d), 8.32 (1H, d), 8.82 (1H, dd)   438               78                                 (300 MHz, CDCl 3 ) δ 2.51 (3H, s), 4.20 (2H, s), 7.01 (1H, d), 7.17 (1H, t), 7.34-7.46 (2H, m), 7.57-7.62 (2H, m), 8.10-8.17 (2H, m), 8.40 (1H, s), 8.85 (2H, dd)   421               79                                 (300 MHz, CD 3 OD) δ 2.53 (3H, s), 4.23 (2H, s), 7.16-7.23 (3H, m), 7.54-7.59 (2H, m), 7.84 (1H, dd), 8.04 (2H, bs), 8.25 (1H, bs), 8.85 (2H, dd)   439               80                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.89 (3H, s), 4.18 (2H, s), 6.85-6.90 (1H, m),6.95- 7.08 (3H, m), 7.25-7.28 (1H, m), 7.36- 7.44 (2H, m), 7.97 (1H, dd), 8.10 (1H, s), 8.13-8.18 (2H, m), 8.92 (1H, dd), 10.05 (1H, bs)   425               81                                 (300 MHz, CDCl 3 ) δ 2.34 (3H, s), 3.95 (2H, s), 6.50 (1H, d), 6.56-6.57 (1H, m), 6.79 (1H, dd), 6.91 (1H, d), 7.25-7.33 (2H, m), 7.78 (1H, m), 7.91-7.97 (2H, m), 8.03 (1H, s), 8.81 (1H, d), 10.80 (1H, bs), 11.48 (1H, bs)   411               82                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.19 (2H, s), 6.98 (1H, d), 7.25-7.30 (2H, m), 7.37- 7.45 (2H, m), 7.68 (1H, dd), 7.97 (1H, dd), 8.11-8.19 (3H, m), 8.40 (1H, d), 8.93 (1H, dd)   412               83                                 (300 MHz, CDCl 3 ) δ 2.45 (3H, s), 4.21 (2H, s), 6.96 (1H, d), 7.22-7.27 (2H, m), 7.36- 7.44 (2H, m), 7.66 (1H, dt), 7.98 (1H, dd), 8.10-8.19 (3H, m), 8.50 (1H, dd), 8.60 (1H, dd), 8.92 (1H, dd), 11.40 (1H, bs)   378               84                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.24 (2H, s), 6.97 (1H, d), 7.14 (1H, d), 7.24-7.29 (3H, m), 7.33-7.44 (3H, m), 7.98 (1H, d), 8.12 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.11 (1H, bs)   461               85                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.25 (2H, s), 6.99 (1H, d), 7.14 (1H, d), 7.24-7.28 (1H, m), 7.32-7.43 (4H, m), 8.14 (2H, s), 8.41 (1H, s), 8.85 (2H, dd)   462               86                                 (300 MHz, CDCl 3 ) δ 2.33 (6H, s), 2.52 (3H, s), 2.75 (2H, t), 4.14 (2H, t), 4.18 (2H, s), 6.87-6.92 (1H, m), 6.95-7.08 (3H, m), 7.24 (1H, s), 7.35-7.44 (2H, m), 7.98 (1H, dd), 8.10-8.18 (3H, m), 8.92 (1H, dd), 9.85 (1H, bs)   482               87                                 (300 MHz, CDCl 3 ) δ 1.78 (4H, pentet), 2.51 (3H, s), 2.63 (4, td), 2.93 (2H, t), 4.16 (2H, s), 7.18 (2H, t), 6.85-6.90 (1H, m), 6.94-7.07 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.41 (1H, dd), 7.97 (1H, dd), 8.09-8.18 (3H, m), 8.92 (1H, dd), 10.01 (1H, bs)   508               88                                 (300 MHz, CDCl 3 ) δ 2.51 (3H, s), 2.57 (4H, t), 2.81 (2H, t), 3.70 (4H, t), 4.16 (2H, t), 4.17 (2H, s), 6.86-6.91 (1H, m), 6.95- 7.08 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.42 (1H, dd), 7.97 (1H, dd), 8.10-8.18 (3H, m), 8.92 (1H, dd), 9.98 (1H, bs)   524               89                                 (300 MHz, CDCl 3 ) δ 2.00 (2H, pentet), 2.24 (6H, s), 2.47 (2H, t), 2.50 (3H, s), 4.09 (2H, t), 4.16 (2H, s), 6.84-6.88 (1H, m), 6.95-7.07 (3H, m), 7.24 (1H, s), 7.35- 7.44 (2H, m), 7.97 (1H, dd), 8.10-8.18 (3H, m), 8.92 (1H, dd)   496               90                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 3.31 (2H, bs), 3.83 (2H, t), 4.10 (2H, s), 6.56-6.60 (1H, m), 6.76 (1H, d), 6.87-6.96 (2H, m), 7.22 (1H, d), 7.34-7.42 (2H, m), 7.93 (1H, d), 8.09 (1H, d), 8.15 (2H, bs), 8.90 (1H, dd), 10.45 (1H, bs)   454               91                                 (300 MHz, CDCl 3 ) δ 2.46 (3H, s), 3.90 (2H, t), 4.10 (2H, t), 4.12 (2H, s), 6.81-6.86 (1H, m), 6.93-7.00 (3H, m), 7.24 (1H, s), 7.67- 7.43 (2H, m), 7.94 (1H, dd), 8.10 (1H, d), 8.16 (2H, bs), 8.91 (1H, dd), 10.88 (1H, bs)   455               92                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.43 (3H, s), 3.75 (2H, t), 4.16 (2H, s), 4.18 (2H, t), 6.86-6.91 (1H, m), 6.94-7.08 (3H, m), 7.24 (1H, s), 7.36 (1H, s), 7.42 (1H, dd), 7.98 (1H, dd), 8.11 (1H, d), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.22 (1H, bs)   469               93                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.74 (3H, s), 4.16 (2H, s), 4.71 (2H, s), 6.91-6.97 (3H, m), 7.06 (1H, td), 7.24 (1H, s), 7.37 (1H, d), 7.42 (1H, dd), 7.97 (1H, d), 8.10-8.18 (3H, m), 8.92 (1H, dd), 10.35 (1H, bs)   483               94                                 (300 MHz, CDCl 3 ) δ 2.40 (3H, s), 3.91 (2H, t), 4.09 (2H, t), 4.11 (2H, s), 6.78-6.83 (1H, m), 6.91-6.99 (3H, m), 7.34 (1H, d), 7.43 (1H, t), 8.15 (2H, s), 8.38 (1H, s), 8.84 (2H, s), 11.25 (1H, bs)   456               95                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.43 (3H, s), 3.76 (2H, t), 4.16 (2H, s), 4.18 (2H, t), 6.87-6.91 (1H, m), 6.96-7.08 (3H, m), 7.31 (1H, d), 7.40 (1H, t), 8.14 (2H, s), 8.42 (1H, s), 8.84 (2H, dd), 10.30 (1H, bs)   470               96                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.09 (2H, t), 4.04 (2H, t), 4.16 (2H, s), 6.85-6.90 (1H, m), 6.95-7.07 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.41 (1H, dd), 7.97 (1H, dd), 8.09-8.18 (3H, m), 8.92 (1H, dd), 10.40 (1H, bs)   454               97                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.15 (2H, s), 4.51 (2H, s), 5.80 (N − H, 1H, bs), 6.71 (N − H, 1H, bs), 6.63-7.06 (4H, m), 7.25- 7.28 (1H, m), 7.37-7.44 (2H, m), 7.94 (1H, dd), 8.10 (1H, d), 8.16-8.18 (2H, m), 8.91 (1H, dd), 11.00 (1H, bs)   468               98                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.57 (3H, s), 4.04 (N − H, 1H, bs), 4.75 (N − H, 1H, bs), 6.86 (1H, bs), 7.11 (2H, d), 7.23 (1H, d), 7.46-7.53 (2H, m), 7.85 (1H, dd), 8.05 (1H, d), 8.20 (1H, bs), 8.25 (1H, d), 8.87 (1H, dd)   469               99                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.09 (2H, t), 4.05 (2H, t), 4.16 (2H, s), 6.85-6.90 (1H, m), 6.95-7.07 (3H, m), 7.30 (1H, d), 7.40 (1H, t), 8.13 (2H, s), 8.41 (1H, s), 8.84 (2H, dd)   455               100                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.77 (3H, s), 4.16 (2H, s), 4.71 (2H, s), 6.92-6.99 (3H, m), 7.04-7.10 (1H, m), 7.33 (1H, d), 7.41 (1H, t), 8.13 (2H, s), 8.40 (1H, s), 8.84 (2H, dd)   484               101                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.48 (3H, s), 4.05 (2H, s), 4.63 (2H, s), 6.84-6.89 (1H, m), 6.93-7.04 (3H, m), 7.22 (1H, d), 7.45 (1H, t), 7.94 (1H, dd), 8.01 (1H, d), 8.22 (1H, d), 8.76 (2H, dd)   470               102                                 (300 MHz, CDCl 3 ) δ 2.49 (3H, s), 4.15 (2H, s), 4.52 (2H, s), 5.82 (N − H, 1H, bs), 6.76 (N − H, 1H, bs), 6.93-7.07 (4H, m), 7.33 (1H, d), 7.42 (1H, t), 8.13 (2H, s), 8.38 (1H, s), 8.84 (2H, dd)   469               103                                 (300 MHz, CDCl 3 ) δ 2.59 (3H, s), 4.37 (2H, s), 6.98 (1H, d), 7.25-7.28 (2H, m), 7.32 (1H, d), 7.37-7.44 (2H, m), 7.64 (1H, t), 7.97 (1H, dd), 8.11 (1H, d), 8.15-8.18 (2H, m), 8.92 (1H, dd), 11.05 (1H, bs)   412               104                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.48 (3H, s), 4.15 (2H, s), 6.97 (1H, d), 7.05 (1H, dd), 7.14 (1H, d), 7.35-7.42 (2H, m), 7.47- 7.52 (1H, m), 7.83 (1H, dd), 7.90 (1H, dd), 8.01 (1H, d), 8.08 (1H, d), 8.16 (1H, dd), 8.80 (1H, dd)   439               105                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.49 (3H, s), 4.17 (2H, s), 6.98 (1H, d), 7.08 (1H, dd), 7.13 (1H, d), 7.35-7.41 (2H, m), 7.45- 7.50 (1H, m), 7.81 (1H, dd), 7.97-8.01 (2H, m), 8.05 (1H, d), 8.13 (1H, dd), 8.80 (1H, dd)   463               106                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 3.39 (3H, s), 3.56 (2H, q), 3.67 (2H, dt), 4.23 (2H, s), 6.95 (1H, d), 7.08 (1H, dd), 7.23 (1H, s), 7.35-7.49 (3H, m), 7.96 (1H, dd), 8.06- 8.11 (2H, m), 8.16-8.18 (2H, m), 8.92 (1H, dd), 10.70 (1H, bs)   496               107                                 (300 MHz, CDCl 3 ) δ 2.37 (3H, s), 3.57 (2H, q), 3.79 (2H, t), 4.15 (2H, s), 6.91 (1H, dd), 6.96 (1H, d), 7.04-7.15 (1H, m), 7.20- 7.30 (1H, m), 7.37-7.43 (2H, m), 7.80 (1H, dd), 7.85 (1H, dd), 8.04 (1H, d), 8.10 (1H, d), 8.14 (1H, dd), 8.90 (1H, dd)   482               108                                 (300 MHz, CDCl 3  + CD 3 OD) δ 2.49 (3H, s), 3.87 (2H, s), 4.17 (2H, s), 6.95-7.01 (2H, m), 7.17-7.33 (3H, m), 7.35-7.43 (2H, m), 7.96 (1H, d), 8.08-8.17 (3H, m), 8.91 (1H, dd), 10.40 (1H, bs)   424               109                                 (300 MHz, CDCl 3 ) δ 2.42 (3H, s), 4.08 (2H, s), 4.58 (2H, s), 6.89 (1H, dd), 6.97 (1H, d), 7.13-7.18 (1H, m), 7.22-7.26 (2H, m), 7.38- 7.43 (2H, m), 7.93 (1H, dd), 8.08 (1H, d), 8.13-8.15 (2H, m), 8.91 (1H, dd), 11.20 (1H, bs)   425               110                                 (300 MHz, CDCl 3 ) δ 1.99 (4H, m), 2.54 (3H, s), 3.23 (4H, t), 4.31 (2H, s), 6.37 (1H, dd), 6364 (1H, d), 6.95 (1H, d), 7.23-7.43 (5H, m), 7.98 (1H, dd), 8.08-8.17 (3H, m), 8.91 (1H, dd), 10.40 (1H, bs)   446               111                                 (300 MHz, CDCl 3 ) δ 2.52 (3H, s), 4.27 (2H, s), 7.19 (1H, d), 7.39 (1H, dd), 7.58- 7.64 (1H, m), 7.72-7.77 (1H, m), 8.04 (2H, bs), 8.14 (1H, dd), 8.24 (1H, s), 8.84 (2H, dd)   441               112                                 (300 MHz, CDCl 3 ) δ 2.50 (3H, s), 4.09 (2H, s), 6.64-6.72 (2H, m), 6.91-6.98 (2H, m), 7.31 (1H, d), 7.39 (1H, t), 8.13 (2H, d), 8.41 (1H, s), 8.84 (2H, dd)   411               113                                 (300 MHz, CDCl 3 ) δ 2.57 (3H, s), 4.40 (2H, s), 6.97 (1H, d), 7.19-7.26 (2H, m), 7.35- 7.42 (3H, m), 7.67 (1H, td), 7.96 (1H, dd), 8.08 (1H, d), 8.14-8.16 (2H, m), 8.65 (1H, d), 8.90 (1H, dd), 11.00 (1H, bs)   378               114                                 (300 MHz, CDCl 3 ) δ 2.48 (3H, s), 4.16 (2H, s), 6.96 (1H, d), 7.15-7.26 (3H, m), 7.36- 7.50 (4H, m), 7.96 (1H, dd), 8.11 (1H, d), 8.17 (2H, m), 8.92 (1H, dd), 10.40 (1H, br s)   456               115                                 (300 MHz, CDCl 3 ) δ 4.18 (2H, s), 7.07- 7.11 (1H, m), 7.23 (2H, m), 7.40-7.51 (5H, m), 7.97 (1H, dd), 8.12-8.19 (3H, m), 8.48 (1H, m), 8.93 (1H, dd)   442               116                                 (300 MHz, CDCl 3 ) δ 3.91 (3H, s), 4.20 (2H, s), 6.57 (1H, d), 7.05 (1H, d), 7.26 (2H, m), 7.36-7.44 (2H, m), 7.51 (2H, m), 7.99 (1H, dd), 8.11-8.18 (3H, m), 8.92 (1H, dd)   472                    
The chemical names of the compounds listed in the Table 1 are as follows:
         1. 6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   2. 6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   3. 6-(2-(3-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   4. 6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   5. 6-(5-(6-methylpyridin-2-yl)-2-(3-(methylsulfonyl)benzyl)-1H-imidazol-4-yl)quinoline   6. 6-(5-(6-bromopyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   7. 6-(5-(6-bromopyridin-2-yl)-2-(3-fluorobenzyl)-1H-imidazol-4-yl)quinoline   8. 6-(2-(3-bromobenzyl)-5-(6-bromopyridin-2-yl)-1H-imidazol-4-yl)quinoline   9. 6-(5-(6-bromopyridin-2-yl)-2-(3-chlorobenzyl)-1H-imidazol-4-yl)quinoline   10. 2-methyl-6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   11. 6-(2-(3-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   12. 6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   13. 6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   14. 2-methyl-6-(5-(6-methylpyridin-2-yl)-2-(3-(methylsulfonyl)benzyl)-1H-imidazol-4-yl)quinoline   15. 6-(5-(6-bromopyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)-2-methylquinoline   16. 6-(2-(3-bromobenzyl)-5-(6-bromopyridin-2-yl)-1H-imidazol-4-yl)-2-methylquinoline   17. 6-(5-(6-bromopyridin-2-yl)-2-(3-chlorobenzyl)-1H-imidazol-4-yl)-2-methylquinoline   18. 6-(5-(6-bromopyridin-2-yl)-2-(3-fluorobenzyl)-1H-imidazol-4-yl)-2-methylquinoline   19. 2-(4-(4-methoxyphenyl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   20. 2-(2-(3-chlorobenzyl)-4-(4-methoxyphenyl)-1H-imidazol-5-yl)-6-methylpyridine   21. 2-(4-(4-chlorophenyl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   22. 2-(4-(4-chlorophenyl)-2-(3-fluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   23. 2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-5-yl)-6-methylpyridine   24. 2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-chlorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   25. 2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(3-fluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   26. 6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   27. 6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   28. 6-(2-(3-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   29. 6-(5-(6-chloropyridin-2-yl)-2-(3-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   30. 6-(2-(3-chlorobenzyl)-5-(6-chloropyridin-2-yl)-1H-imidazol-4-yl)quinoline   31. 2-chloro-6-(2-(3-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   32. 6-(2-(2-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   33. 6-(2-(4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   34. 6-(5-(6-methylpyridin-2-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-4-yl)quinoline   35. 6-(2-(2-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   36. 6-(2-(4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   37. 6-(5-(6-methylpyridin-2-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-4-yl)quinoxaline   38. 6-(2-(3,4-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   39. 6-(2-(3-bromo-4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   40. 6-(5-(6-methylpyridin-2-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   41. 6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoline   42. 6-(2-(3,5-bis(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   43. 6-(2-(4-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   44. 6-(2-(3,5-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   45. 6-(2-(2,3-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   46. 6-(2-(4-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   47. 6-(2-(3-fluoro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-H-imidazol-4-yl)quinoline   48. 6-(2-(3-chloro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   49. 6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoline   50. 6-(2-(2,3-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   51. 6-(2-(3,4-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   52. 6-(2-(3,5-difluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   53. 6-(2-(2-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   54. 6-(2-(4-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   55. 6-(5-(6-methylpyridin-2-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   56. 6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)quinoxaline   57. 6-(2-(3,5-bis(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   58. 6-(2-(3-bromo-4-fluorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   59. 6-(2-(3-fluoro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   60. 6-(2-(4-chlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   61. 6-(2-(2,3-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   62. 6-(2-(3,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   63. 6-(2-(2,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   64. 6-(2-(3-chloro-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   65. 6-(5-(6-methylpyridin-2-yl)-2-(4-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoxaline   66. 6-(2-(3-bromo-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   67. 6-(5-(6-methylpyridin-2-yl)-2-(3-phenoxybenzyl)-1H-imidazol-4-yl)quinoxaline   68. 6-(2-(2-fluoro-3-(trifluoromethyl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   69. 6-(2-(2,4-dichlorobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   70. 6-(2-(3-bromo-4-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   71. 2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(2,4,5-trifluorobenzyl)-1H-imidazol-5-yl)-6-methylpyridine   72. 6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   73. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline   74. 6-(2-(4-chloro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   75. 2-chloro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline   76. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile   77. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   78. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzonitrile   79. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   80. 6-(2-(4-fluoro-3-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   81. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol   82. 6-(2-((6-chloropyridin-3-yl)methyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   83. 6-(5-(6-methylpyridin-2-yl)-2-(pyridin-3-ylmethyl)-1H-imidazol-4-yl)quinoline   84. 6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoline   85. 6-(5-(6-methylpyridin-2-yl)-2-(3-(trifluoromethoxy)benzyl)-1H-imidazol-4-yl)quinoxaline   86. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)-N,N-dimethylethanamine   87. 6-(2-(4-fluoro-3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   88. 4-(2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethyl)morpholine   89. 3-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)-N,N-dimethylpropan-1-amine   90. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenylamino)ethanol   91. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanol   92. 6-(2-(4-fluoro-3-(2-methoxyethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   93. Methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate   94. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanol   95. 6-(2-(4-fluoro-3-(2-methoxyethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   96. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanamine   97. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetamide   98. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetic acid   99. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethanamine   100. methyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetate   101. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetic acid   102. 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)acetamide   103. 6-(2-((6-chloropyridin-2-yl)methyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   104. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzoic acid   105. 6-(2-(4-fluoro-3-(1H-tetrazol-5-yl)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   106. 2-fluoro-N-(2-methoxyethyl)-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   107. 2-fluoro-N-(2-hydroxyethyl)-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)benzamide   108. (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanamine   109. (2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenyl)methanol   110. 6-(5-(6-methylpyridin-2-yl)-2-(3-(pyrrolidin-1-yl)benzyl)-1H-imidazol-4-yl)quinoline   111. 6-(2-(4-fluoro-3-nitrobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline   112. 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)aniline   113. 6-(5-(6-methylpyridin-2-yl)-2-(pyridin-2-ylmethyl)-1H-imidazol-4-yl)quinoline   114. 6-(2-(4-bromobenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline   115. 6-(2-(4-bromobenzyl)-5-(pyridin-2-yl)-1H-imidazol-4-yl)quinoline   116. 6-(2-(4-bromobenzyl)-5-(6-methoxypyridin-2-yl)-1H-imidazol-4-yl)quinoline       

     Biological Data 
     The biological activity of the compounds of the invention may be assessed using the following assays: 
     Cell-Free Assay for Evaluating Inhibition of ALK5 Kinase Phosphorylation of Smad3 
     The His-tagged, constitutively active ALK5 (T204D) and Smad3 full protein were expressed in insect cells using the Invitrogen BacNBlue baculovirus expression system. Expressed proteins were purified with Qiagen Ni-NTA resin column. The purified smad3 protein 200 ng was mixed with 100 μL of 0.1 M sodium bicarbonate coating buffer and coated into Flash-Plates by pipetting. Plates were covered and incubated at 4° C. for 16 hours. Then the plates were washed 3 times with 200 μL of coating buffer and allowed to block in 1% BSA in PBS at room temperature for 1 hour. The purified ALK5 protein 100 ng was mixed with 100 μL of reaction buffer containing 20 mM Tris-HCl (pH 7.4), 5 mM MgCl 2 , 1 mM CaCl 2 , 1 mM DTT, 1 μM ATP and 2 μCi γ- 32 p-ATP, and 1 μL of each test compound of formula (I) prepared in 100% DMSO solution at different concentrations. The assay was then initiated with the addition of ALK5 reaction mixture into Smad3-coated Flash-Plates, followed by incubation at 30° C. for 3 hours. After incubation, the assay buffer was removed and washed 3 times with 200 μL of 10 mM sodium pyrophosphate solution. Then, the Flash-Plates were air-dried and counted on a Packard TopCount. 
     Compounds of formula (I) typically exhibited IC 50  values of less than 10 μM; some exhibited IC 50  values of less than 1 μM; and some even exhibited IC 50  values less than 50 nM. 
     Cell-Free Assay for Evaluating Inhibition of ALK4 Kinase Phosphorylation of Smad3 
     Inhibition of the ALK4 kinase phosphorylation of Smad3 by test compounds of formula (□) can be determined in a similar manner to that described above for ALK5 inhibition except that a similarly His-tagged ALK4 is used in place of the His-tagged, constitutively active ALK5. 
     Compounds of formula (□) typically exhibited IC 50  values of less than 10 μM; some exhibited IC 50  values of less than 1 μM. 
     Assay for Evaluating Cellular Inhibition of TGF-β Signaling 
     Biological activity of the compounds of formula (□) was determined by measuring their ability to inhibit TGF-β1-induced Smad binding element-luciferase (SBE-Luc) reporter activity and PAI-1-luciferase (p3TP-Lux) reporter activity in HepG2 cells. HepG2 cells were transiently transfected with either SBE-Luc reporter construct or p3TP-Lux reporter construct grown in DMEM medium containing 10% FBS, penicillin 100 U/mL, streptomycin 100 μg/mL, L-glutamine 2 mM, sodium pyruvate 1 mM, and non-essential amino acids. The transfected cells were then plated at a concentration of 2.5×10 4  cells/well in 96 well plates and starved for 3-6 hours in media with 0.5% FBS at 37□ in a 5% CO 2  incubator. The cells were then stimulated with 5 ng/mL TGF-β1 ligand in the starvation media containing 1% DMSO either in the presence or absence of a test compound of formula (□) and incubated at 37□ in a 5% CO 2  incubator for 24 hours. The media was washed out, and the luciferase activity in cell lysates was determined by using a luciferase assay system (Promega). 
     Compounds of formula (□) typically exhibited IC 50  values of less than 10 μM; some exhibited IC 50  values of less than 1 μM; and some even exhibited IC 50  values of less than 50 μM. 
       FIG. 1  shows effect of the compounds of Examples 32, 45, 73, 79, and 83 on TGF-β1-induced 3TP-Luc reporter activity in HepG2 cells.
2-pyridyl substituted imidazoles of the formula (I) as shown in claim 1, are provided, which are useful in the treatment of diseases mediated by ALK5 or ALK4 inhibitors or both.