Antiviral compounds

Abstract

Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).

1 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
   A-L-Y  (I)
   wherein: L is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         A is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted aryl(C 1-2  alkyl), an optionally substituted heteroaryl and an optionally substituted heterocyclyl; 
         Y is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl; 
         R 1a , R 1b , R 1c  and R 1d  are each independently hydrogen or an unsubstituted C 1-4  alkyl; 
         R 2a , R 2a1 , R 2b , R 2b1 , R 2c , R 2c1 , R 2d  and R 2d1  are each independently selected from the group consisting of hydrogen, an optionally substituted C 1-4  alkyl, an optionally substituted aryl(C 1-6  alkyl), an optionally substituted heterocyclyl(C 1-6  alkyl), an alkoxyalkyl, an aminoalkyl, a hydroxyalkyl and hydroxy; or 
         R 2a1  is hydrogen, and R 1a  and R 2a  is joined together with the atoms to which they are attached to form an optionally substituted 5 membered heterocyclyl or an optionally substituted 6 membered heterocyclyl, R 2b1  is hydrogen, and R 1b  and R 2b  is joined together with the atoms to which they are attached to form an optionally substituted 5 membered heterocyclyl or an optionally substituted 6 membered heterocyclyl; 
            between X 1a  and X 2a  represents a single or double bond between X 1a  and X 2a ;   between X 2a  and X 3a  represents a single or double bond between X 2a  and X 3a ; provided that   between X 1a  and X 2a  and   between X 2a  and X 3a  cannot be both double bonds and at least one of   is a double bond; 
         when   between X 1a  and X 2a  represents a double bond and   between X 2a  and X 3a  is a single bond, then X 1a  is N or CR 4a1 , X 2a  is N or CR 5a  and X 3a  is NR 6a1 , C(═O) or CR 6a2 R 6a3 ; and when   between X 1a  and X 2a  represents a single bond and   between X 2a  and X 3a  is a double bond, then X 1a  is NR 4a  or CR 4a2 R 4a3 , X 2a  is N or CR 5a  and X 3a  is N or CR 6a ; or 
         X 1a , X 2a  and X 3a  are each independently C, N, O or C(═O), and form a ring or ring system selected from an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl by joining X 1a  and X 3a  together; with the proviso that the valencies of X 1a , X 2a  and X 3a  can be each independently satisfied with a substituent selected from hydrogen and an optionally substituted C 1-4  alkyl, and X 1a , X 2a  and X 3a  are uncharged; 
         R 3a  and R 3a1  are each independently selected from the group consisting of hydrogen, hydroxy, halogen, amino, an optionally substituted C 1-4  alkyl, an optionally substituted C 2-4  alkenyl, an optionally substituted C 2-4  alkynyl, an optionally substituted C 3-6  cycloalkyl, an optionally substituted C 1-4  alkoxy, —O-carboxy, an optionally substituted heteroaryl, an optionally NH 2  substituted heterocyclyl, CHF 2 , CF 3  and 
       
       
         
           
           
               
               
           
         
       
       provided that R 3a  and R 3a1  cannot be both hydrogen; or R 3a  and R 3a1  together form ═N—OR 3a ; or R 3a  and R 3a1  together with the atom to which they are attached can be joined to form an optionally substituted 3 membered ring, an optionally substituted 4 membered ring, an optionally substituted 5 membered ring or an optionally substituted 6 membered ring;
 R 4a , R 4a1 , R 4a2  and R 4a3  are each independently hydrogen or an unsubstituted C 1-4  alkyl; 
 R 5a  and R 5a1  are each independently be hydrogen or an unsubstituted C 1-4  alkyl; 
 R 6a  and R 6a1  are each independently hydrogen, an optionally substituted C 1-4  alkyl or an optionally substituted alkoxyalkyl; 
 R 6a2  and R 6a3  are each independently hydrogen or an unsubstituted C 1-4  alkyl; 
 X 1b , X 2b  and X 3b  are each independently C, N, O or C(═O), and form indicates a bi-cyclic ring selected from an optionally substituted bi-cyclic heteroaryl and an optionally substituted bi-cyclic heterocyclyl by joining X 1b  and X 3b  together, wherein   between X 1b  and X 2b  represents a single or double bond between X 1b  and X 2b ;   between X 2b  and X 3b  represents a single or double bond between X 2b  and X 3b ; and provided that at least one of X 1b , X 2b  and X 3b  comprises a nitrogen atom and both   cannot be double bonds; with the proviso that the of X 2b  and X 3b  can be each valencies of X 1b , X 2b  and X 3b  can be each independently satisfied with a substituent selected from hydrogen and an optionally substituted C 1-4  alkyl; and X 1b , X 2b  and X 3b  are uncharged; 
 R 3c  and R 3c1  are each independently selected from the group consisting of hydrogen, hydroxy, halogen, amino, an optionally substituted C 1-4  alkyl, an optionally substituted C 2-4  alkenyl, an optionally substituted C 2-4  alkynyl, an optionally substituted C 3-6  cycloalkyl, an optionally substituted C 1-4  alkoxy, —O-carboxy, an optionally substituted heteroaryl, an optionally NH 2  substituted heterocyclyl, CHF 2 , CF 3  and 
 
       
         
           
           
               
               
           
         
       
       provided that R 3c  and R 3c1  cannot be both hydrogen; or R 3c  and R 3c1  together form ═N—OR c ; or R 3c  and R 3c1  together with the atom to which they are attached can be joined to form an optionally substituted 3 membered ring, an optionally substituted 4 membered ring, an optionally substituted 5 membered ring or an optionally substituted 6 membered ring;
 R a  and R c  are each independently hydrogen or an unsubstituted C 1-4  alkyl; 
 R 4c  and R 5  are taken together to form an unsubstituted aryl, an unsubstituted heteroaryl or an optionally substituted heterocyclyl; 
 Z c  is N or CH; 
 m d  is 0 or 1; and 
 ring B d  is an optionally substituted C 5  cycloalkyl; 
 ring B d1  is an optionally substituted pyridinyl; and 
 provided that when L is Formula (IIc), then Y is absent; and 
 provided that the compound is not 
 
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , wherein L is Formula (Ia). 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The compound of  claim 2 , wherein L is Formula (Ia1): 
       
         
           
           
               
               
           
         
       
     
     
         10 . (canceled) 
     
     
         11 . The compound of  claim 9 , wherein X 1a , X 2a  and X 3a  is a ring or ring system is an optionally substituted mono-cyclic heteroaryl or an optionally substituted bi-cyclic heteroaryl. 
     
     
         12 . The compound of  claim 9 , wherein X 1a , X 2a  and X 3a  is a ring or ring system is an optionally substituted mono-cyclic heterocyclyl or an optionally substituted bi-cyclic heterocyclyl. 
     
     
         13 . The compound of  claim 9 , wherein X 1a , X 2a  and X 3a  is a ring or ring system selected from the group consisting of an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted S 
       
         
           
           
               
               
           
         
       
       an optionally substituted an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       and an optionally substituted 
       
         
           
           
               
               
           
         
       
       wherein R A1 , R A2 , R A3  and R A4  is each independently hydrogen or an unsubstituted C 1-6  alkyl; each   is independently absent or a bond; each R A5 , each R A6 , each R A7  is an unsubstituted C 1-6  alkyl, halogen, hydroxy, amino, mono-substituted amino, di-substituted amino or —NH—S(═O)C 1-4  alkyl; and R A8  is hydrogen or an unsubstituted C 1-6  alkyl. 
     
     
         14 . The compound of  claim 2 , wherein L is Formula (Ia2): 
       
         
           
           
               
               
           
         
         wherein R 7a1 , R 7a2  and R 7a3  are each independently selected from the group consisting of hydrogen, halogen, hydroxy, an optionally substituted C 1-8  alkyl, an optionally substituted C 2-8  alkenyl, an optionally substituted C 2-8  alkynyl, an optionally substituted C 3-6  cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted hydroxyalkyl, an optionally substituted C 1-8  alkoxy, an optionally substituted alkoxyalkyl, amino, mono-substituted amino, di-substituted amino, halo(C 1-8  alkyl), haloalkyl, an optionally substituted O-amido and an optionally substituted C-carboxy. 
       
     
     
         15 . (canceled) 
     
     
         16 . The compound of  claim 14 , wherein R 7a1  is a hydrogen, R 7a2  is an optionally substituted C 1-4  alkyl, and R 7a3  is hydrogen 
     
     
         17 . The compound of  claim 16 , wherein the substituted C 1-4  alkyl of R 7a2  is substituted with a substituent selected from the group consisting of halo, hydroxy, C 1-4  alkoxy, an optionally substituted aryl(C 1-4  alkyl), an optionally substituted C-carboxy, amino, an optionally substituted mono-substituted amino, an optionally substituted di-substituted amino, an optionally substituted C-amido, an optionally substituted N-amido, an optionally substituted N-carbamyl, an optionally substituted N-sulfonamido, an optionally substituted urea, an optionally substituted amidine and an optionally substituted acetylurea. 
     
     
         18 . The compound of  claim 14 , wherein R 7a1  is a hydrogen, R 7a2  is an optionally substituted heterocyclyl, and R 7a3  is hydrogen 
     
     
         19 . (canceled) 
     
     
         20 . The compound of  claim 2 , wherein L is Formula (Ia3): 
       
         
           
           
               
               
           
         
         wherein the dashed semi-circle along with the two carbon atoms to which it is connected form an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted heterocyclyl; and R 8a3  is selected from the group consisting of hydrogen, halogen, hydroxy, an optionally substituted C 1-8  alkyl, an optionally substituted C 2-8  alkenyl, an optionally substituted C 2-8  alkynyl, an optionally substituted C 3-6  cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted hydroxyalkyl, an optionally substituted C 1-8  alkoxy, an optionally substituted alkoxyalkyl, amino, mono-substituted amino, di-substituted amino, halo(C 1-8  alkyl), haloalkyl and an optionally substituted C-carboxy. 
       
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The compound of  claim 20 , wherein the dashed semi-circle along with the two carbon atoms to which it is connected form an optionally substituted 5-membered heterocyclyl or an optionally substituted 6-membered heterocyclyl. 
     
     
         25 . The compound of  claim 20 , wherein the dashed semi-circle along with the two carbon atoms to which it is connected form an optionally substituted 
       
         
           
           
               
               
           
         
       
       an optionally substituted 
       
         
           
           
               
               
           
         
       
       or an optionally substituted 
       
         
           
           
               
               
           
         
       
       wherein each   is independently absent or a bond; each R A5 , each R A6 , each R A7  is halogen, an unsubstituted C 1-6  alkyl, hydroxy, amino, an optionally substituted mono-substituted amino, an optionally substituted di-substituted amino, —(CH 2 ) 1-4 OH, —(CH 2 ) 1-4 NH 2  or N-sulfinamido (for example, —NH—S(═O)C 1-4  alkyl), or two R A5 , two R A6  or two R A7  are taken together to form an optionally substituted 5-membered ring to an optionally substituted 6-membered ring; and R A8  is hydrogen or an unsubstituted C 1-6  alkyl. 
     
     
         26 . The compound of  claim 2 , wherein R 1a  can be hydrogen. 
     
     
         27 . (canceled) 
     
     
         28 . The compound of  claim 2 , wherein R 2a  and R 2a1  are both hydrogen. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . The compound of  claim 2 , wherein R 3a  is hydroxy, and R 3a1  is selected from the group consisting of amino, an unsubstituted C 1-4  alkyl, an unsubstituted C 2-4  alkenyl, an unsubstituted C 2-4  alkynyl, an unsubstituted C 3-6  cycloalkyl, an unsubstituted C 1-4  alkoxy, hydroxy, halogen, —O-carboxy, an unsubstituted heteroaryl, an optionally substituted heterocyclyl CHF and CF 3 . 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . The compound of  claim 2 , wherein R 3a  is hydroxy, and R 3a1  is CF 3 . 
     
     
         40 . The compound of  claim 2 , wherein R 3a  is hydroxy, and R 3a1  is CHF 2 . 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . The compound of  claim 2 , wherein one of R 3a  and R 3a1  is a substituted C 1-4  alkyl substituted with a substituent selected from the group consisting of halogen, hydroxy, amino, mono-substituted amino, di-substituted amino, —N-amido, an optionally substituted mono-cyclic heteroaryl and an optionally substituted mono-cyclic heterocyclyl; and the other of R 3a  and R 3a1  is hydroxy. 
     
     
         50 . (canceled) 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . The compound of  claim 1 , wherein L is Formula (Ib): 
       
         
           
           
               
               
           
         
       
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . (canceled) 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . (canceled) 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . (canceled) 
     
     
         64 . (canceled) 
     
     
         65 . (canceled) 
     
     
         66 . (canceled) 
     
     
         67 . (canceled) 
     
     
         68 . (canceled) 
     
     
         69 . (canceled) 
     
     
         70 . (canceled) 
     
     
         71 . (canceled) 
     
     
         72 . (canceled) 
     
     
         73 . (canceled) 
     
     
         74 . (canceled) 
     
     
         75 . (canceled) 
     
     
         76 . (canceled) 
     
     
         77 . (canceled) 
     
     
         78 . (canceled) 
     
     
         79 . (canceled) 
     
     
         80 . (canceled) 
     
     
         81 . (canceled) 
     
     
         82 . (canceled) 
     
     
         83 . (canceled) 
     
     
         84 . (canceled) 
     
     
         85 . (canceled) 
     
     
         86 . (canceled) 
     
     
         87 . (canceled) 
     
     
         88 . (canceled) 
     
     
         89 . (canceled) 
     
     
         90 . (canceled) 
     
     
         91 . (canceled) 
     
     
         92 . (canceled) 
     
     
         93 . (canceled) 
     
     
         94 . (canceled) 
     
     
         95 . (canceled) 
     
     
         96 . (canceled) 
     
     
         97 . (canceled) 
     
     
         98 . (canceled) 
     
     
         99 . (canceled) 
     
     
         100 . (canceled) 
     
     
         101 . (canceled) 
     
     
         102 . (canceled) 
     
     
         103 . (canceled) 
     
     
         104 . (canceled) 
     
     
         105 . The compound of  claim 1 , wherein A is an optionally substituted aryl. 
     
     
         106 . The compound of  claim 105 , wherein A is an optionally substituted phenyl. 
     
     
         107 . The compound of  claim 106 , wherein A is a phenyl substituted with one or more substituents selected from the group consisting of: an unsubstituted C 1-4  alkyl, an optionally substituted C 1-4  alkyl, cycloalkyl, hydroxy, an optionally substituted C 1-4  alkoxy, C 1-4  alkoxy, halogen, haloalkyl, an optionally substituted haloalkoxy, nitro, amino, mono-substituted amino, di-substituted amine, —O-amido, sulfenyl, alkyoxyalkyl, an optionally substituted aryl, an optionally substituted mono-cyclic heteroaryl, an optionally substituted mono-cyclic heterocyclyl, an optionally substituted aryl(C 1-4  alkyl), an optionally substituted monocyclic heteroaryl(C 1-4  alkyl), an optionally substituted monocyclic heterocyclyl(C 1-4  alkyl), hydroxyalkyl and aminoalkyl. 
     
     
         108 . The compound of  claim 106 , wherein A is a phenyl substituted with one or more substituents selected from the group consisting of: methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, t-butoxy, phenoxy, bromo, chloro, fluoro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyano, N,N-di-methyl-amine, N,N-di-ethyl-amine, N-methyl-N-ethyl-amine, N-methyl-amino, N-ethyl-amino, amino, N-amido, N-sulfonamido, alkylthio, an optionally substituted phenyl, an optionally substituted imidazole, an optionally substituted morpholinyl, an optionally substituted pyrazole, an optionally substituted pyrrolidinyl, an optionally substituted pyridinyl, an optionally substituted piperidinyl, an optionally substituted piperidinone, an optionally substituted pyrrolidinone, an optionally substituted pyrimidine, an optionally substituted pyrazine, an optionally substituted 1,2,4-oxadiazole, —(CH 2 ) 1-4 —OH, —(CH 2 ) 1-2 —NH(CH 3 ), an optionally substituted —(CH 2 ) 1-2 -imidazole, an optionally substituted —(CH 2 ) 1-2 -pyrrolidinone, an optionally substituted —(CH 2 ) 1-2 -imidazolidinone, —O(CH 2 ) 2 —NH 2 , —O(CH 2 ) 2 —NH(CH 3 ), —O(CH 2 ) 2 —N(CH 3 ) 2 , —O—(CH 2 ) 2-4 OH, —O(CH 2 ) 2 OCH 3 , an optionally substituted —O(CH 2 ) 0-2 -cyclopentanone, an optionally substituted —O(CH 2 ) 0-2 pyrrolidinone, an optionally substituted —O(CH 2 ) 0-2 -morpholinyl, an optionally substituted —O(CH 2 ) 0-2 -triazole, an optionally substituted —O(CH 2 ) 0-2 -imidazole, an optionally substituted —O(CH 2 ) 0-2 -pyrazole, an optionally substituted —O(CH 2 ) 0-2 -tetrahydrofuran, an optionally substituted —O(CH 2 ) 0-2 -pyrrolidinone, an optionally substituted —O(CH 2 ) 0-2 -tetrazole, an optionally substituted —O(CH 2 ) 0-2 -tetrazolone, 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         109 . The compound of  claim 106 , wherein A is a di-substituted phenyl. 
     
     
         110 . (canceled) 
     
     
         111 . (canceled) 
     
     
         112 . (canceled) 
     
     
         113 . (canceled) 
     
     
         114 . (canceled) 
     
     
         115 . (canceled) 
     
     
         116 . The compound of  claim 1 , wherein Y is an optionally substituted aryl. 
     
     
         117 . The compound of  claim 116 , wherein Y is a mono-substituted phenyl. 
     
     
         118 . The compound of  claim 117 , wherein Y is a di-substituted phenyl. 
     
     
         119 . (canceled) 
     
     
         120 . (canceled) 
     
     
         121 . (canceled) 
     
     
         122 . (canceled) 
     
     
         123 . (canceled) 
     
     
         124 . (canceled) 
     
     
         125 . (canceled) 
     
     
         126 . (canceled) 
     
     
         127 . The compound of  claim 1 , wherein Y is unsubstituted. 
     
     
         128 . The compound of  claim 1 , wherein Y is substituted with one or more R B , wherein each R B  is independently selected from the group consisting of: cyano, halogen, an optionally substituted C 1-4  alkyl, an unsubstituted C 2-4  alkenyl, an unsubstituted C 2-4  alkynyl, an optionally substituted aryl, an optionally substituted 5 or 6 membered heteroaryl, an optionally substituted 5 or 6 membered heterocyclyl, hydroxy, C 1-4  alkoxy, alkoxyalkyl, C 1-4  haloalkyl, haloalkoxy, an unsubstituted acyl, an optionally substituted —C-carboxy, an optionally substituted —C-amido, sulfonyl, carbonyl, amino, mono-substituted amine, di-substituted amine and 
       
         
           
           
               
               
           
         
       
     
     
         129 . (canceled) 
     
     
         130 . (canceled) 
     
     
         131 . The compound of  claim 1 , wherein the compound of Formula (I) is selected from the group consisting of: 1, 13-1, 100, 101, 102, 103, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 116a, 116b, 117, 117a, 117b, 118, 118a, 118b, 119, 120, 120a, 120b, 121, 122, 122a, 122b, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 138, 139, 142, 143, 144, 145, 146, 147, 148, 151, 152, 153, 154, 155, 158, 159, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 218, 219, 221, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 306, 307, 308, 309, 310, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,492, 493, 494, 495, 496, 497, 498a, 498b, 498c, 498d, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604a, 604b, 604c, 604d, 605a, 605b, 605c, 605d, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623a, 623b, 624a, 624b, 625, 626, 627, 628, 629, 630, 631, 632, 633a, 633b, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 680, 681 and 682, or a pharmaceutically acceptable salt of the foregoing. 
     
     
         132 . The compound of  claim 1 , wherein the compound of Formula (I) is selected from the group consisting of: 104, 130, 135, 136, 137, 140, 141, 149, 150, 156, 157, 160, 161,217, 220, 222, 229, 287, 302, 303,304, 305, 311, 401, 473 and 474, or a pharmaceutically acceptable salt of the foregoing. 
     
     
         133 . (canceled) 
     
     
         134 . (canceled) 
     
     
         135 . (canceled) 
     
     
         136 . A pharmaceutical composition comprising an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof. 
     
     
         137 . (canceled) 
     
     
         138 . (canceled) 
     
     
         139 . (canceled) 
     
     
         140 . (canceled) 
     
     
         141 . (canceled) 
     
     
         142 . (canceled) 
     
     
         143 . (canceled) 
     
     
         144 . The compound of  claim 1  having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         145 . The compound of  claim 1  having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         146 . The compound of  claim 1 , wherein the compound of Formula (I) is selected from the group consisting of: 605d, 630, 650, 653, 664 and 682, or a pharmaceutically acceptable salt of the foregoing. 
     
     
         147 . A method of ameliorating or treating a paramyxovirus viral infection that can include administering to a subject suffering from the paramyxovirus viral infection an effective amount of one or more compounds of Formula (I), or a pharmaceutically acceptable salt thereof. 
     
     
         148 . A method of ameliorating or treating a paramyxovirus viral infection that can include contacting a cell infected with the paramyxovirus with an effective amount of one or more compounds of Formula (I), or a pharmaceutically acceptable salt thereof. 
     
     
         149 . The method of  claim 148 , wherein the paramyxovirus infection is a human respiratory syncytial virus infection. 
     
     
         150 . A method for inhibiting viral replication of a paramyxovirus, which can comprise contacting a cell infected with the virus with an effective amount of one or more compounds of Formula (I), or a pharmaceutically acceptable salt thereof. 
     
     
         151 . The method of  claim 149 , further comprising contacting the cell with an effective amount with one or more anti-RSV agents, wherein the one or more anti-RSV agents is selected from the group consisting of an anti-RSV antibody, a fusion protein inhibitor, an N-protein inhibitor, a RSV polymerase inhibitor, an IMPDH inhibitor, an interferon and an other compound that inhibits the RSV virus, or a pharmaceutically acceptable salt of any of the foregoing. 
     
     
         152 . The method of  claim 151 , wherein the one or more agents is selected from the group consist of RSV-IGIV, palivizumab, motavizumab, 1-cyclopropyl-3-[[1-(4-hydroxybutyl)benzimidazol-2-yl]methyl]imidazo[4,5-c]pyridin-2-one (BMS-433771), 4,4″-bis-{4,6-bis-[3-(bis-carbamoylmethyl-sulfamoyl)-phenylamino]-(1,3,5)triazin-2-ylamino}-biphenyl-2,2″-disulfonic-acid (RFI-641), 4,4′-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfonilimino]-1,3,5-triazine-2-ylamino]-biphenyl-2,2′-disulfonic acid, disodium salt (CL387626), 2-[[2-[[1-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]-6-methyl-3-pyridinol (JNJ-2408068), 2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl]amino]methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol (TMC-353121), 5,5′-bis[1-(((5-amino-1H-tetrazolyl)imino)methyl)]2,2′,4″-methylidynetrisphenol (VP-14637, MDT-637), N-(2-hydroxyethyl)-4-methoxy-N-methyl-3-(6-methyl-[1,2,4]triazolo[3,4-a]phthalazin-3-yl)benzenesulfonamide (P13), 2-((2-((1-(2-aminoethyl)piperidin-4-yl)amino)-4-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6-methylpyridin-3-ol (R170591), 1,4-bis(3-methylpyridin-4-yl)-1,4-diazepane (C15), (R)-9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-2,3-dihydro-1H-imidazo[1′,2′:1,2]pyrrolo[3,4-c]pyridin-5(9bH)-one (BTA9981), [2,2-bis(docosyloxy-oxymethyl)propyl-5-acetaoamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium-oxysulfonyl)-D-glycero-D-galacto-2-nonulopyranosid]onate (MBX-300), BTA-C286, N-(2-((S)-2-(5-((S)-3-aminopyrrolidin-1-yl)-6-methylpyrazolo[1,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-4-chlorophenyl)methanesulfonamide (GS-5806), an anti-RSV nanobody, a peptide fusion inhibitor (such as a peptide having the sequence DEFDASISQVNEKINQSLAFIRKSDELL (T-67), a peptide having the sequence FDASISQVNEKINQSLAFIRKSDELLHNVNAGKST (T-118), (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (RSV-604), STP-92, iKT-041, 6-{4-[(biphenyl-2-ylcarbonyl)amino]benzoyl}-N-cyclopropyl-5,6-dihydro-4H-thieno[3,2-d][1]benzazepine-2-carboxamide (YM-53403). N-cyclopropyl-5-(4-(2-(pyrrolidin-1-yl)benzamido)benzoyl)-5,6,7,10-tetrahydrobenzo[b]cyclopenta[d]azepine-9-carboxamide. 6-(4-(2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)nicotinamido)benzoyl)-N-cyclopropyl-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, 4-amino-8-(3-{[2-(3,4-dimethoxyphenyl)ethyl]amino}propyl)-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-1H-imidazo[4,5-h]-isoquinoline-7,9(6H, 8H)-dione, AZ27, ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydiofuran-2-yl)-1H-1,2,4-triazole-3-carboximidamide (Taribavirin, viramidine), 1,3,4-thiadiazol-2-ylcyanamide (LY253963), tetrahydrofuran-3-yl-3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate (VX-497), (4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid (Mycophenolic acid), 2-morpholin-4-ylethyl-(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate (Mycophenolate Mofetil), a Type 1 interferon, a Type 2 interferon, a Type 3 interferon, a double stranded RNA oligonucleotide, 5-methyl-N-[4-(trifluoromethyl)phenyl]-isoxazole-4-carboxamide (leflumomide), N-(2-chloro-4-methylphenyl)-2-((1-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)thio)propanamide (JMN3-003), an intratracheal formulation of recombinant human CC10 (CG-100), high titer, human immunoglobulin (RI-001), a non-neutralizing mAb against the G protein (mAb 131-2G), ALN-RSV01, ALN-RSV02, Medi-559, Medi-534 and Medi-557, or a pharmaceutically acceptable salt of the foregoing.