US2004019067A1PendingUtilityA1
Kinase inhibitors

Assignee: AMGEN INCPriority: Jan 22, 1999Filed: Oct 22, 2002Published: Jan 29, 2004
Est. expiryJan 22, 2019(expired)· nominal 20-yr term from priority
Inventors:David M. Armistead Jean E. Bemis Daniel Elbaum Gregory Habgood Perry M. Novak Joseph J. Nunes Leticia M. Toledo-Sherman
C07D 239/56C07D 239/70C07D 239/47
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References
Claims
Abstract

The invention relates to inhibitors of kinases, compositions comprising the inhibitors, and methods of using the inhibitors and inhibitor compositions. The inhibitors and compositions comprising them are useful for treating disease or disease symptoms. The invention also provides for methods of making kinase inhibitor compounds, methods of inhibiting kinase activity, and methods for treating disease or disease symptoms.
Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is H; CN; COOR 5 ; C(O)NR 5 R 5 ; halo; C1-C10 alkyl; C1-C10 alkenyl; C1-C10 alkyl substituted with 1-3 independent NR 5 R 5 , NR 5 R 6 , SR 5  or OR 5 ; or C1-C10 alkenyl substituted with 1-3 independent NR 5 R 5 , NR 5 R 6 , SR 5  or OR 5 ;  
 R 2  is NR 5 R 5 ; SR 5 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 15 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with 1-3 independent aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with 1-3 independent aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 R 3  is phenyl substituted with 1-3 independent R 4 ; R 8 ; COOR 5 ; or C1-C10 alkyl substituted with 1-3 independent aryl, R 7  or R 8 ;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with 1-3 independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with 1-3 independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with 1-3 independent aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2  R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with 1-3 independent R 7 , R 9  or aryl; or C1-C10 alkenyl substituted with 1-3 independent R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with 1-3 independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with 1-3 independent aryl, R 7  or R 9 ;  
 Each R 16  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; C1-C10 alkyl substituted with 1-3 independent aryl, R 7  or R 9  groups; C1-C10 alkenyl substituted with 1-3 independent aryl, R 7  or R 9 ; or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group; and  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 .  
 
     
     
         2 . The compound of  claim 1  having the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is H; COOR 5 ; C(O)NR 5 R 5 ; halo; C2-C10 alkyl; C1-C10 alkenyl; C1-C10 alkyl substituted with NR 5 R 5 , NR 5 R 6 , SR 5  or OR 5 ; or C1-C10 alkenyl substituted with NR 5 R 5 , NR 5 R 6 , SR 5  or OR 5 ;  
 R 2  is NR 5 R 15 ; SR 5 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 16 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 R 3  is phenyl substituted with 1-3 independent R 4 ; R 8 ; COOR 5 ; or C1-C10 alkyl substituted with aryl, R 7  or R 8 ;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5  R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2 R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 16  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C1-C10 alkenyl substituted with aryl, R 7  or R 9 ; or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 .  
 
     
     
         3 . The compound of  claim 1  having the formula,  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is CN;  
 R 2  is NR 5 R 15 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 16 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2  R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 9 R 19 , COOR 19 , NO 2 , CN;  
 Each R 14  is each independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 16  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C1-C10 alkenyl substituted with aryl, R 7  or R 9 ; or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ;  
 Each R 17  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 ;  
 wherein when all R 4  and R 17  are simultaneously H, R 14  may not be Me, Cl, OMe or NO 2 ; and wherein R 14  and R 17  may not simultaneously be Cl.  
 
     
     
         4 . The compound of  claim 1  having the formula,  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is CN;  
 R 2  is NR 5 R 15 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 16 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2 R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13  SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 14  is independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 16  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C1-C10 alkenyl substituted with aryl, R 7  or R 9 ; or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 ;  
 wherein when all R 4  are H, R 14  may not be Me or OMe.  
 
     
     
         5 . The compound of  claim 1  having the formula,  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is CN;  
 R 2  is NR 5 R 15 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 16 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2  R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 14  is independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 16  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 17  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 ;  
 wherein R 14  and R 17  may not simultaneously be Cl and wherein R 14  may not simultaneously be methyl when all R 4  and R 17  are H.  
 
     
     
         6 . The compound of  claim 1  having the formula,  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is CN;  
 R 2  is NR 5 R 15 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 16 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 R 3  is R 8 ; COOR 5 ; or C1-C10 alkyl substituted with R 7 , R 8 , or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; wherein R 3  is not unsubstituted furanyl, unsubstituted thienyl or unsubstituted pyridyl;  
 X is O or S;  
 Each R 4  is independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2  R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 15  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 16  is independently C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C1-C10 alkenyl substituted with aryl, R 7  or R 9 ; or phenyl substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 , C1-C10 alkyl substituted with R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 .  
 
     
     
         7 . A compound of formula,  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 2  is NR 5 R 5 ; SR 5 ; OR 5 ; R 8 ; aryl; N(R 5 )—N═CH(R 8 ); N(R 5 )—N═CH(aryl); NR 5 —NR 5 C(O)NR 5 R 5 ; NR 5 —NR 5 R 15 ; NR 5 —NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ; or C1-C10 alkenyl substituted with aryl, R 8 , halo, CF 3 , SR 5 , OR 5 , OC(O)R 5 , NR 5 R 5 , NR 5 R 6 , COOR 5 , NO 2 , CN, C(O)R 5 , C(O)NR 5 R 5 , or S(O) 2 NR 5 R 5 ;  
 X is O or S;  
 R 4  is one, two, or three substituents, each independently selected from H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 8 ; halo; haloalkyl; CF 3 ; SR 5 ; OR 5 ; NR 5 R 5 ; NR 5 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)C(O)R 5 ; C(O)NR 5 R 5 ; OC(O)R 5 ; S(O) 2 R 5 ; S(O) 2 NR 5 R 5 ; NR 5 C(O)NR 5 R 5 ; NR 5 C(O)C(O)R 5 ; NR 5 C(O)R 5 ; NR 5 (COOR 5 ); NR 5 C(O)R 8 ; NR 5 S(O) 2 NR 5 R 5 ; NR 5 S(O) 2 R 5 ; NR 5 S(O) 2 R 8 ; NR 5 C(O)C(O)NR 5 R 5 ; NR 5 C(O)C(O)NR 5 R 6 ; C1-C10 alkyl substituted with aryl, R 7  or R 8 ; or C1-C10 alkenyl substituted with aryl, R 7  or R 8 ;  
 Each R 5  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; C1-C10 alkyl substituted with one or two independent aryl, R 7  or R 9  groups; C3-C10 cycloalkyl substituted with one or two independent aryl, R 7  or R 9  groups; or C1-C10 alkenyl substituted with aryl, R 7  or R 9 ;  
 Each R 6  is independently C(O)R 5 , COOR 5 , or S(O) 2 R 5 ;  
 Each R 7  is independently halo, CF 3 , SR 10 , OR 10 , OC(O)R 10 , NR 10 R 10 , NR 10 R 11 , NR 11 R 11 , COOR 10 , NO 2 , CN, C(O)R 10 , or C(O)NR 10 R 10 ;  
 Each R 8  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; aryl; R 9 ; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 5 ; OR 5 ; OC(O)R 5 ; NR 5 R 5 ; NR 5 R 6 ; NR 6 R 6 ; COOR 5 ; NO 2 ; CN; C(O)R 5 ; C(O)NR 5 R 5 ; C1-C10 alkyl substituted with R 7 , R 9  or aryl; C1-C10 alkenyl substituted with R 7 , R 9  or aryl;  
 Each R 9  is independently a 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, which may be saturated or unsaturated, and wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent independently selected from C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; halo; sulfur; oxygen; CF 3 ; haloalkyl; SR 10 ; OR 10 ; NR 10 R 10 ; NR 10 R 11 ; NR 11 R 11 ; COOR 10 ; NO 2 ; CN; C(O)R 10 ; or C(O)NR 10 R 10 ;  
 Each R 10  is independently H, C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; haloalkyl; C1-C10 alkyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ; or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 11  is independently C(O)R 10 , COOR 10 , or S(O) 2 R 10 ;  
 Each R 12  is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, or phenyl optionally substituted with 1-3 independent C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C4-C10 cycloalkenyl, halo, CF 3 , OR 13 , SR 13 , NR 13 R 13 , COOR 13 , NO 2 , CN, C(O)R 13 , C(O)NR 13 R 13 , NHC(O)R 13 , or OC(O)R 13 ;  
 Each R 13  is independently H; C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; C1-C10 alkyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN; or phenyl optionally substituted with halo, CF 3 , OR 19 , SR 19 , NR 19 R 19 , COOR 19 , NO 2 , CN;  
 Each R 18  is independently C1-C10 alkyl or both R 18  may be taken together as a C2-C7 alkyl chain; wherein any R 18  may optionally be substituted with 1-3 independent R 7  or R 8 ;  
 Each R 19  is independently H; C1-C10 alkyl; C3-C10 cycloalkyl or phenyl;  
 Each haloalkyl is independently a C1-C10 alkyl substituted with one or more halogen atoms, selected from F, Cl, Br, or I, wherein the number of halogen atoms may not exceed that number that results in a perhaloalkyl group;  
 Each aryl is independently a 6-carbon monocyclic or 10-carbon bicyclic aromatic ring system optionally substituted with 1-3 independent C1-C10 alkyl; C2-C10 alkenyl; C2-C10 alkynyl; C3-C10 cycloalkyl; C4-C10 cycloalkenyl; R 9 ; halo; haloalkyl; CF 3 ; OR 12 ; SR 12 ; NR 12 R 12 ; COOR 12 ; NO 2 ; CN; C(O)R 12 ; C(O)C(O)R 12 ; C(O)NR 12 R 12 ; S(O) 2 R 12 ; N(R 12 )C(O)R 12 ; N(R 12 )(COOR 12 ); N(R 12 )S(O) 2 R 12 ; S(O) 2 NR 12 R 12 ; OC(O)R 12 ; NR 12 C(O)NR 12 R 12 ; NR 12 C(O)C(O)R 12 ; NR 12 C(O)R 9 ; NR 12 S(O) 2 NR 12 R 12 ; NR 12 S(O) 2 R 9 ; NR 12 C(O)C(O)NR 12 R 12 ; C1-C10 alkyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; C2-C10 alkenyl substituted with 1-3 independent R 9 , halo, CF 3 , OR 12 , SR 12 , NR 12 R 12 , COOR 12 , NO 2 , CN, C(O)R 12 , C(O)NR 12 R 12 , NHC(O)R 12 , NH(COOR 12 ), S(O) 2 NR 12 R 12 , OC(O)R 12 ; or R 12 .  
 
     
     
         8 . A composition comprising a compound according to any of claims  1 - 7  and a pharmaceutically acceptable carrier.  
     
     
         9 . A method of treating a kinase mediated disease or disease symptoms in a mammal comprising administration to said mammal of a compound of any of claims  1 - 7 .  
     
     
         10 . A method of inhibiting kinase activity in a mammal comprising the step of administering to said mammal a compound of any of claims  1 - 7 .  
     
     
         11 . A method of making a compound of any of claims  1 - 7  comprising reacting a pyrimidinone of the formula:  
       
         
           
           
               
               
           
         
       
       with an appropriate nucleophilic agent, wherein the groups in said formula are as defined in any of claims  1 - 7 .  
     
     
         12 . The method of  claim 11 , wherein R 1  is CN; R 3  is as defined in any of claims  1 - 7 ; X is O; and R 5  is Me.
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