Antiviral compounds
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Human Respiratory Syncytial Virus (HRSV) or Human Metapneumovirus (HMPV) inhibitors. The present invention further relates to pharmaceutical compositions comprising the compounds of Formula (I) for administration to a subject suffering from HRSV or HMPV infection. The invention also relates to methods of treating an HRSV or HMPV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
1. A compound represented by Formula (V-3):
or a pharmaceutically acceptable salt thereof, wherein:
R 4 is selected from the group consisting of:
1) optionally substituted —C 1 -C 6 alkyl;
2) optionally substituted —C 3 -C 8 cycloalkyl;
3) optionally substituted 3- to 8-membered heterocyclic;
4) optionally substituted aryl;
5) optionally substituted arylalkyl;
6) optionally substituted heteroaryl; and
7) optionally substituted heteroarylalkyl;
R 7 is selected from the group consisting of:
1) hydrogen;
2) halogen;
3) optionally substituted —C 1 -C 6 alkyl;
4) optionally substituted —C 1 -C 6 alkoxy; and
5) optionally substituted —C 3 -C 8 cycloalkyl;
R 6 is selected from the group consisting of:
1) —C(O)NH 2 ;
2) optionally substituted —C 1 -C 8 -alkyl;
3) optionally substituted —C 3 -C 8 -cycloalkyl;
4) hydrogen;
5) optionally substituted 4- and 5-membered heterocyclic ring;
6) —C(O)NHR 11 ; and
7) —C(O)NR 11 R 12 ;
R 11 and R 12 are each independently selected from the group consisting of:
1) optionally substituted —C 1 -C 8 alkyl;
2) optionally substituted —C 2 -C 8 alkenyl;
3) optionally substituted —C 2 -C 8 alkynyl;
4) optionally substituted —C 3 -C 8 cycloalkyl;
5) optionally substituted 3- to 8-membered heterocycloalkyl;
6) optionally substituted aryl;
7) optionally substituted arylalkyl;
8) optionally substituted heteroaryl; and
9) optionally substituted heteroarylalkyl;
alternatively, R 11 and R 12 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic ring;
each R 21 is independently optionally substituted methyl, halo, —CN, —OR 31 , or —NR 31 R 32 ;
R 23 is hydrogen, halo, —OR 31 , optionally substituted —C 1 -C 6 alkyl, or optionally substituted —C 3 -C 8 -cycloalkyl;
R 24 is optionally substituted —C 1 -C 6 alkyl, or optionally substituted —C 3 -C 8 -cycloalkyl;
each R 31 and R 32 is independently selected from the group consisting of hydrogen; optionally substituted —C 1 -C 8 -alkyl; optionally substituted —C 3 -C 8 -cycloalkyl; optionally substituted 4- to 8-membered heterocyclic; optionally substituted aryl; optionally substituted arylalkyl;
optionally substituted heteroaryl; and optionally substituted heteroarylalkyl; and
n is 1, 2, 3, 4 or 5.
2. The compound of claim 1 , wherein R 4 is selected from one of the following:
3. The compound of claim 1 , wherein R 6 is selected from the groups below:
4. The compound of claim 1 , selected from the compounds set forth below, or a pharmaceutically acceptable salt thereof:
Compound
Structure
1
2
3
4
5
6
7
9
10
11
12
13
14
15
16
17
18
20
21
22
24
25
26
27
28
29
30
31
32
33
34
36
38
39
40
41
43
47
50
52
53
54
55
58
60
61
62
63
67
68
70
74
75
76
77
79
80
82
83
84
85
86
87
88
90
91
92
94
96
97
98
99
100
103
104
105
109
110
111
113
114
116
117
118
119
120
121
122
123
124
125
127
128
132
133
134
136
137
138
140
141
142
144
145
146
148
149
150
152
153
154
156
158
159
160
161
162
164
165
166
167
168
169
170
171
172
173
174
177
179
180
182
183
185
186
188
189
190
191
192
193
194
195
196
197
198
199
200
5. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
6. A method of treating or preventing a respiratory syncytial virus (RSV) infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , further comprising the step of administering to the subject an additional anti-RSV agent.
8. The method of claim 6 , further comprising administering to the subject a steroid anti-inflammatory compound.
9. A method of treating an RSV infection and influenza in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 and a therapeutically effective amount of an anti-influenza agent.
10. The method of claim 7 , wherein the compound and the anti-RSV agent are co-formulated.
11. The method of claim 7 , wherein the compound and the anti-RSV agent are co-administered.
12. A method of treating or preventing a human metapneumovirus (HMPV) infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .
13. The method of claim 12 , further comprising the step of administering to the subject an anti-HMPV agent.
14. The method of claim 13 , wherein the compound and the anti-HMPV agent are co-formulated.
15. The method of claim 13 , wherein the compound and the anti-HMPV agent are co-administered.