# US 8,785,487 B2 · Hepatitis C virus inhibitors

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- Number: US 8,785,487 B2
- Document ID: US8785487B2
- Status: Granted
- Kind: B2
- Application number: 13/013,212
- Filed: 2011-01-25
- Published: 2011-08-04
- Granted: 2014-07-22
- Earliest claimed: 2010-01-25
- Assignees: Enanta Pharmaceuticals, Inc.
- Applicants: Yao-Ling Qiu; Ce Wang; Xiaowen Peng; Lu Ying; Hui Cao; Yat Sun Or
- Inventors: Yao-Ling Qiu; Ce Wang; Xiaowen Peng; Lu Ying; Hui Cao; Yat Sun Or
- Web page: https://patentgrep.com/patent/US8785487B2

## CPC

- C07D 498/18: Bridged systems
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B—W (I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

## Claims

### Claim 1

A compound represented by Formula (I):
Q-G-A-L-B—W (I)
or a pharmaceutically acceptable salt thereof, wherein:
A and B are each independently absent or a monocyclic or polycyclic group independently selected from the group consisting of aryl, heteroaryl, heterocyclic, C3-C8 cycloalkyl, and C3-C8 cycloalkenyl, each optionally substituted;
L is absent or an aliphatic group;
wherein at least one of A, B and L is present;
W is
G is an optionally substituted 5-membered heteroaryl containing one or more nitrogen atoms, or an optionally substituted 5-membered heteroaryl fused to a mono- or bicyclic ring, wherein the mono- or bicyclic ring is aromatic or non-aromatic, wherein the mono- or bicyclic ring is attached to one of groups A, L and B and wherein the 5-membered heteroaryl contains one or more nitrogen atoms;
Q is hydrogen or
X1 is N;
X2 is N(R1);
R1 is hydrogen;
R11 at each occurence is independently hydrogen, halogen or optionally substituted C1-C4 alkyl;
Y at each occurence is independently C(O);
L1-L2-L3 is a linker selected from:
wherein RX is hydrogen, amino, hydroxy, protected amino or O(C1-C4alkyl); RY is hydrogen or C1-C8 alkyl;
R3 and R4 are hydrogen;
R5 is hydrogen
Alternatively R3, R4 and R5 are taken together with the carbon atom and nitrogen atom to which they are attached to form
U is selected from C(R7)2 and C═C(R2)2;
R2 at each occurrence is independently hydrogen, halogen, optionally substituted C1-C4 alkyl, optionally substituted aryl, or optionally substituted heteroaryl;
R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, O(C1-C4 alkyl), S(C1-C4 alkyl), amino optionally substituted with one or two C1-C4 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C1-C4 alkyl, and optionally substituted C3-C8 cycloalkyl;
Alternatively two geminal R7 groups are taken together with the carbon atom to which they are attached to form a spiro, optionally substituted 3- to 7-membered cyclic group selected from the group consisting of C3-C7 cycloalkyl, C3-C7 cycloalkenyl or 3- to 7-membered heterocyclic;
R7a and R7b at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted aryl, optionally substituted C1-C4 alkyl, and optionally substituted C3-C8 cycloalkyl;
Alternatively, CHR7a—U or CHR7b—U are taken together to form a group selected from CH═CH, fused and optionally substituted C3-C8 cycloalkyl, fused and optionally substituted aryl, or fused and optionally substituted heterocyclic; and
R6 at each occurrence is independently selected from the group consisting of O(C1-C8 alkyl), amino, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted;
wherein heteroaryl refers to a mono- or polycyclic aromatic radical having one or more ring atom selected from S, O and N; and the remaining ring atoms are carbon, wherein any N or S contained within the ring may be optionally oxidized;
“heterocyclic” refers to a non-aromatic ring or a bi- or tri-cyclic group fused system, where (i) each ring system contains at least one heteroatom independently selected from oxygen, sulfur and nitrogen, (ii) each ring system can be saturated or unsaturated (iii) the nitrogen and sulfur heteroatoms may optionally be oxidized, (iv) the nitrogen heteroatom may optionally be quaternized, (v) any of the above rings may be fused to an aromatic ring, and (vi) the remaining ring atoms are carbon atoms which may be optionally oxo-substituted; and
“substituted” refers to substitution by independent replacement of one, two, or three or more of the hydrogen atoms with substituents selected from —F, —Cl, —Br, —I, —OH, protected hydroxy, —NO2, —N3, —CN, —NH2, protected amino, oxo, thioxo, —NH—C1-C12-alkyl, —NH—C2-C8-alkenyl, —NH—C2-C8-alkynyl, —NH—C3-C12-cycloalkyl, —NH-aryl, —NH-heteroaryl, -dialkylamino, -diarylamino, -diheteroarylamino, —O—C1-C12-alkyl, —O—C2-C8-alkenyl, —O—C2-C8-alkynyl, —O—C3-C12-cycloalkyl, —O-aryl, —O-heteroaryl, —C(O)—C1-C12-alkyl, —C(O)—C2-C8-alkenyl, —C(O)—C2-C8-alkynyl, —C(O)—C3-C12-cycloalkyl, —C(O)-aryl, —C(O)-heteroaryl, —CONH2, —CONH—C1-C12-alkyl, —CONH—C2-C8-alkenyl, —CONH—C2-C8-alkynyl, —CONH—C3-C12-cycloalkyl, —CONH-aryl, —CONH-heteroaryl, —OCO2—C1-C12-alkyl, —OCO2—C2-C8-alkenyl, —OCO2—C2-C8-alkynyl, —OCO2—C3-C12-cycloalkyl, —OCO2-aryl, —OCO2-heteroaryl, —CO2—C1-C12 alkyl, —CO2—C2-C8 alkenyl, —CO2—C2-C8 alkynyl, CO2—C3-C12-cycloalkyl, —CO2- aryl, CO2-heteroaryl, CO2-heterocyloalkyl, —OCONH2, —OCONH—C1-C12-alkyl, —OCONH—C2-C8-alkenyl, —OCONH—C2-C8-alkynyl, —OCONH—C3-C12-cycloalkyl, —OCONH-aryl, —OCONH-heteroaryl, —NHC(O)H, —NHC(O)—C1-C12-alkyl, —NHC(O)—C2-C8-alkenyl, —NHC(O)—C2-C8-alkynyl, —NHC(O)—C3-C12-cycloalkyl, —NHC(O)-aryl, —NHC(O)-heteroaryl, —NHCO2—C1-C12-alkyl, —NHCO2—C2-C8-alkenyl, —NHCO2—C2-C8-alkynyl, —NHCO2—C3-C12-cycloalkyl, —NHCO2-aryl, —NHCO2-heteroaryl, —NHC(O)NH2, —NHC(O)NH—C1-C12-alkyl, —NHC(O)NH—C2-C8-alkenyl, —NHC(O)NH—C2-C8-alkynyl, —NHC(O)NH—C3-C12-cycloalkyl, —NHC(O)NH-aryl, —NHC(O)NH-heteroaryl, NHC(S)NH2, —NHC(S)NH—C1-C12-alkyl, —NHC(S)NH—C2-C8-alkenyl, —NHC(S)NH—C2-C8-alkynyl, —NHC(S)NH—C3-C12-cycloalkyl, —NHC(S)NH-aryl, —NHC(S)NH-heteroaryl, —NHC(NH)NH2, —NHC(NH)NH—C1-C12-alkyl, —HC(NH)NH—C2-C8-alkenyl, —NHC(NH)NH—C2-C8-alkynyl, —NHC(NH)NH—C3-C12-cycloalkyl, —NHC(NH)NH-aryl, —NHC(NH)NH-heteroaryl, —NHC(NH)—C1-C12-alkyl, —NHC(NH)—C2-C8-alkenyl, —NHC(NH)—C2-C8-alkynyl, —NHC(NH)—C3-C12-cycloalkyl, —NHC(NH)-aryl, —NHC(NH)-heteroaryl, —C(NH)NH—C1-C12-alkyl, —C(NH)NH—C2-C8-alkenyl, —C(NH)NH—C2-C8-alkynyl, —C(NH)NH—C3-C12-cycloalkyl, —C(NH)NH-aryl, —C(NH)NH-heteroaryl, —S(O)—C1-C12-alkyl, —S(O)—C2-C8-alkenyl, —S(O)—C2-C8-alkynyl, —S(O)—C3-C12-cycloalkyl, —S(O)-aryl, —S(O)-heteroaryl, —SO2NH2, —SO2NH—C1-C12-alkyl, —SO2NH—C2-C8-alkenyl, —SO2NH—C2-C8-alkynyl, —SO2NH—C3-C12-cycloalkyl, —SO2NH-aryl, —SO2NH-heteroaryl, —NHSO2—C1-C12-alkyl, —NHSO2—C2-C8-alkenyl, —NHSO2—C2-C8-alkynyl, —NHSO2—C3-C12-cycloalkyl, —NHSO2-aryl, —NHSO2-heteroaryl, —CH2NH2, —CH2SO2CH3, -aryl, -arylalkyl, -heteroaryl, -heteroarylalkyl, —C3-C12-cycloalkyl, polyalkoxyalkyl, polyalkoxy, —methoxymethoxy, -methoxyethoxy, —SH, —S—C1-C12-alkyl, —S—C2-C8-alkenyl, —S—C2-C8-alkynyl, —S—C3-C12-cycloalkyl, —S-aryl, —S-heteroaryl, and methylthio-methyl.

### Claim 2

A compound, represented by Formula (IIa):
or a pharmaceutically acceptable salt thereof;
wherein Q is
and, R3, R4 and R5 are taken together with the carbon atom and nitrogen atom to which they are attached to form
R1 is hydrogen, hydroxy, O(C1-C4 alkyl) or C1-C4 alkyl;
U is C(R7)2;
R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, O(C1-C4 alkyl), S(C1-C4 alkyl), amino optionally substituted with one or two C1-C4 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C1-C4 alkyl, and optionally substituted C3-C8 cycloalkyl;
Alternatively two geminal R7 groups are taken together with the carbon atom to which they are attached to form a spiro, optionally substituted 3- to 7-membered cyclic group selected from the group consisting of C3-C7 cycloalkyl, C3-C7 cycloalkenyl or 3- to 7-membered heterocyclic;
A, L and B are taken together to form a linker selected from one of the groups illustrated below:
X1 is N;
X2 is NH, or NMe;
Y is C(O); and,
G is selected from one of the groups illustrated below:
R7a and R7b are each independently selected from the group consisting of hydrogen, C1-C4 alkyl, and C3-C8 cycloalkyl;
Alternatively, CHR7a—U or CHR7b—U are taken together to form a group selected from CH═CH, fused C3-C8 cycloalkyl, or fused heterocyclic;
Yet alternatively, U, R7a, and R7b are taken together with the carbon atoms to which they are attached to form a bridged, 4- to 7-membered cyclic group selected from the group consisting of C4-C7 cycloalkyl, C4-C7 cycloalkenyl and 4- to 7-membered heterocyclic;
R6 at selected from the group consisting of O(C1-C8 alkyl), amino, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, each optionally substituted; and,
L1-L2-L3 is a linker is selected from:
wherein RX is hydrogen, amino, hydroxy, protected amino or O(C1-C4 alkyl); RY is hydrogen or C1-C8 alkyl.

### Claim 3

A compound represented by Formula (IIa):
or a pharmaceutically acceptable salt thereof;
wherein Q is
and,
R3, R4 and R5 are taken together with the carbon atom and nitrogen atom to which they are attached to form
R1 is hydrogen, hydroxy, O(C1-C4 alkyl) or C1-C4 alkyl;
U is C(R7)2;
R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, O(C1-C4 alkyl), S(C1-C4 alkyl), amino optionally substituted with one or two C1-C4 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C1-C4 alkyl, and optionally substituted C3-C8 cycloalkyl;
Alternatively two geminal R7 groups are taken together with the carbon atom to which they are attached to form a spiro, optionally substituted 3- to 7-membered cyclic group selected from the group consisting of C3-C7 cycloalkyl, C3-C7 cycloalkenyl or 3- to 7-membered heterocyclic;
A, L and B are taken together to form a linker selected from one of the groups illustrated below:
X1 is N;
X2 is NH, or NMe;
Y is C(O); and,
G is selected from one of the groups illustrated below:
R7a and R7b are each independently selected from the group consisting of hydrogen, C1-C4 alkyl, and C3-C8 cycloalkyl;
Alternatively, CHR7a—U or CHR7b—U are taken together to form a group selected from CH═CH, fused C3-C8 cycloalkyl, or fused heterocyclic;
Yet alternatively, U, R7a, and R7b are taken together with the carbon atoms to which they are attached to form a bridged, 4- to 7-membered cyclic group selected from the group consisting of C4-C7 cycloalkyl, C4-C7 cycloalkenyl and 4- to 7-membered heterocyclic;
R6 at selected from the group consisting of O(C1-C8 alkyl), amino, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, each optionally substituted; and,
L1-L2-L3 is a linker is selected from:
wherein RX is hydrogen, amino, hydroxy, protected amino or O(C1-C4 alkyl); RY is hydrogen or C1-C8 alkyl.

### Claim 4

A compound represented by Formula (Va):
wherein:
L1 and L3 at each occurence are each independently a linear aliphatic group, or one of L1 and L3 is a linear aliphatic group and the other one of L1 and L3 is optionally absent;
R6 is C1-C8 alkyl optionally substituted with amino, hydroxy, protected amino, or O(C1-C4 alkyl); wherein protected amino refers to an amino group substituted with a group selected from methoxycarbonyl, t- butoxycarbonyl, 9-fluorenyl-methoxycarbonyl, benzyloxycarbonyl;
U at each occurrence is independently CH2, CHF, CHMe, CF2, C═CH2, C═CF 2, and C(R7)2,
R7 is hydrogen, halogen or optionally substituted C3-C8 cycloalkyl; alternatively the two geminal R7 groups are taken together with the carbon to which they are attached to form a spiro, 3- to 7-membered, C3-C7 cycloalkyl or 3- to 7- membered heterocyclic;
R7a is hydrogen;
R7b is hydrogen, methyl or optionally substituted C3-C8 cycloalkyl;
or alternatively R7a and U or U and R7b are taken together with the carbon atoms to which they are attached to form a fused, optionally substituted cyclopropyl, and the other of R7b or R7a is hydrogen; or yet alternatively U, R7a and R7b are taken together with the carbon to which they are attached to form a bridged, optionally substituted C4-C7 cycloalkyl; or a pharmaceutically acceptable salt thereof;
wherein the term “substituted” refers to substitution by independent replacement of one, two, or three the hydrogen atoms with substituents selected from —F, —Cl, —Br, —I, —OH, —NO2, —N3, —CN, —NH2, oxo, thioxo, —NH—C1-C12-alkyl, —NH—C2-C8-alkenyl, —NH—C2-C8-alkynyl, —NH—C3-C12-cycloalkyl, —O—C1-C12-alkyl, —O—C2-C8-alkenyl, —O—C2-C8-alkynyl, —O—C3-C12-cycloalkyl, —C(O)—C1-C12-alkyl, —C(O)—C2—C8-alkenyl, —C(O)—C2-C8-alkynyl, —C(O)—C3-C12-cycloalkyl, —CONH2, —CONH—C1-C12-alkyl, —CONH—C2-C8-alkenyl, —CONH—C2-C8-alkynyl, —CONH—C3-C12-cycloalkyl, —OCO2—C1-C12-alkyl, —OCO2—C2-C8-alkenyl, —OCO2—C2-C8-alkynyl, —OCO2—C3-C12-cycloalkyl, —CO2—C1-C12 alkyl, —CO2—C2-C8 alkenyl, —CO2—C2-C8 alkynyl, CO2—C3-C12-cycloalkyl, —NHC(O)H, —NHC(O)—C1-C12-alkyl, —NHC(O)—C2-C8-alkenyl, —NHC(O)—C2-C8-alkynyl, —NHC(O)—C3-C12-cycloalkyl, —NHCO2—C1-C12-alkyl, —NHCO2—C2-C8-alkenyl, —NHCO2—C2-C8-alkynyl, —NHCO2—C3-C12-cycloalkyl, —S(O)—C1-C12-alkyl, —S(O)—C2-C8-alkenyl, —S(O)—C2-C8-alkynyl, —S(O)—C3-C12-cycloalkyl, —SH, —S—C1-C12-alkyl, —S—C2-C8-alkenyl, —S—C2-C8-alkynyl, —S—C3-C12-cycloalkyl.

### Claim 5

A compound represented by Formula (VIa) or (VIb):
wherein
A and B are each independently an optionally substituted aryl or optionally substituted heteroaryl;
L is absent or optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
L1 and L3 at each occurence are each independently a linear aliphatic group, or one of L1 and L3 is a linear aliphatic group and the other one of L1 and L3 is optionally absent;
L2 at each occurence is independently absent, or selected from the group consisting of aryl, heteroaryl, heterocyclic, C3-C8 cycloalkyl, and C3-C8 cycloalkenyl, each optionally substituted;
R6 is C1-C8 alkyl optionally substituted with amino, hydroxy, protected amino, or O(C1-C4 alkyl); wherein protected amino refers to an amino group substituted with a group selected from methoxycarbonyl, t- butoxycarbonyl, 9-fluorenyl-methoxycarbonyl, benzyloxycarbonyl;
U at each occurrence is independently CH2, CHF, CHMe, CF2, C═CH2, C═CF2, or C(R7)2,
R7 is hydrogen, halogen or optionally substituted C3-C8 cycloalkyl; alternatively the two geminal R7 groups are taken together with the carbon to which they are attached to form a spiro, 3- to 7-membered, optionally substituted C3-C7 cycloalkyl or optionally substituted 3- to 7-membered heterocyclic;
R7a is hydrogen; and
R7b is hydrogen, methyl or optionally substituted C3-C8 cycloalkyl;
or alternatively R7a and U or U and R7b are taken together with the carbon atoms to which they are attached to form a fused, optionally substituted cyclopropyl, and the other of R7b or R7a is hydrogen; or yet alternatively, U, R7a and R7b are taken together with the carbon atoms to which they are attached to form a bridged, optionally substituted C4-C7 cycloalkyl; or a pharmaceutically acceptable salt thereof;
wherein the term “substituted” refers to substitution by independent replacement of one, two, or three the hydrogen atoms with substituents selected from —F, —Cl, —Br, —I, —OH, —NO2, —N3, —CN, —NH2, oxo, thioxo, —NH—C1-C12-alkyl, —NH—C2-C8-alkenyl, —NH—C2-C8-alkenyl, —NH—C3-C12-cycloalkyl, —O—C1-C12-alkyl, —O—C2-C8-alkenyl, —O—C2-C8-alkynyl, —O—C3-C12-cycloalkyl, —C(O)—C1-12-alkyl, —C(O)—C2-C8-alkenyl, —C(O)—C2-C8-alkynyl, —C(O)—C3-C12-cycloalkyl, —CONH2, —CONH—C1-C12-alkyl, —CONH—C2-C8-alkenyl, —CONH—C2-C8-alkynyl, —CONH—C3-C12-cycloalkyl, —OCO2—C1-C12-alkyl, —OCO2—C2-C8-alkenyl, —OCO2—C2-C8-alkynyl, —OCO2—C3-C12-cycloalkyl, —CO2—C1-C12 alkyl, —CO2—C2-C8 alkenyl, —CO2—C2-C8 alkynyl, —CO2—C3-C12-cycloalkyl, —NHC(O)H, —NHC(O)—C1-C12-alkyl, —NHC(O)—C2-C8-alkenyl, —NHC(O)—C2-C8-alkynyl, —NHC(O)—C3-C12-cycloalkyl, —NHCO2—C1-C12-alkyl, —NHCO2—C2-C8-alkenyl, —NHCO2—C2-C8-alkynyl, —NHCO2—C3-C12-cycloalkyl, —S(O)—C1-C12-alkyl, —S(O)—C2-C8-alkenyl, —S(O)—C2-C8-alkynyl, —S(O)—C3-C12-cycloalkyl, —SH, —S—C1-C12-alkyl, —S—C2-C8-alkenyl, —S—C2-C8-alkynyl, —S—C3-C12-cycloalkyl.

### Claim 6 (depends on 5)

The compound of claim 5, wherein
is selected from:
and L1-L2-L3 is a linker of from 8 to 16 bond lengths and is selected from:
wherein RX is hydrogen, amino, hydroxy, protected amino or O(C1-C4 alkyl); RY is hydrogen or optionally substituted C1-C8 alkyl; each of the above shown groups is further optionally substituted; or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

A compound of claim 1 selected from the group of compounds compiled in the following tables:
Compounds 1-219.
Entry
Entry
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
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
217
218
219
Compounds 220-229.
Entry
R
R′
R″
U
220
Me
H
H
CH2
221
H
H
H
CF2
223
H
H
H
224
H
Me
H
CH2
225
H
H
H
226
H
Ph
H
CH2
227
H
H
H
228
H
H
Ph
CH2
229
H
H
H
Compounds 240-249.
Entry
R
R′
R″
R′′′
240
F
H
H
H
241
F
F
H
H
242
Me
H
H
H
243
Me
Me
H
H
244
H
H
Me
Me
245
H
H
Et
Et
246
CF3
H
H
H
247
CF3
H
CF3
H
248
Cl
H
H
H
249
Cl
H
Cl
H
Compounds 250-264
Entry
R
252
253
254
255
256
257
258
259
260
261
Compounds 334 and 343
346
348
349
352
353
358
359
360
361
Compounds 369

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a compound or a combination of compounds according to claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier or excipient.

### Claim 9 (depends on 1)

A method of treating infection caused by an RNA-containing virus comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound or combination of compounds of claim 1, or a pharmaceutically acceptable salt thereof wherein the RNA-containing virus is hepatitis C virus.

### Claim 10 (depends on 9)

The method of claim 9, further comprising the step of co-administering one or more agents selected from the group consisting of a host immune modulator and an antiviral agent, or a combination thereof.

### Claim 11 (depends on 8)

The pharmaceutical composition of claim 8, further comprising an agent selected from interferon, pegylated interferon, ribavirin, amantadine, an HCV protease inhibitor, an HCV polymerase inhibitor, an HCV helicase inhibitor, or an internal ribosome entry site inhibitor.

### Claim 12 (depends on 8)

The composition of claim 8, further comprising a cytochrome P450 monooxygenase inhibitor or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 11)

The composition of claim 11, wherein the cytochrome P450 mooxygenase inhibitor is ritonavir.

### Claim 14 (depends on 2)

A method of treating hepatitis C infection in a subject in need thereof comprising co-administering to said subject a cytochrome P450 monooxygenase inhibitor or a pharmaceutically acceptable salt thereof, and a compound of claim 2 or a pharmaceutically acceptable salt thereof.

### Claim 15

A compound selected from the group of compounds compiled in the following table or a pharmaceutically acceptable salt thereof:
Compounds 230-239
Entry
R
R′
R″
230
Me
H
H
231
H
CO2Me
H
232
H
F
H
233
H
H
CO2Me
234
H
H
F
235
H
OMe
H
236
H
Cl
H
237
H
H
OMe
238
H
H
Cl
239
H
CF3
H.

### Claim 16

A compound selected from the group of compounds compiled in the following tables or a pharmaceutically acceptable salt thereof:
Compounds 265-282
Entry
Aa
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
Compounds 283-303
Entry
Aa
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297

### Claim 17 (depends on 2)

A compound of claim 2, wherein A, L and B are taken together to form the linker having the structure:

### Claim 18 (depends on 3)

A compound of claim 3, wherein A, L and B are taken together to form the linker having the structure:

### Claim 19 (depends on 6)

A compound of claim 6, wherein
is selected from: