ANTIVIRAL COMPOUNDS
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.