5, 6-D
In one aspect, the invention provides compounds represented by Formula I, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, solvates, and combinations thereof, pharmaceutical compositions comprising these compounds and the use of these compounds for treating a viral infection in a subject.
1. A compound represented by Formula I or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein:
each D represents a position which is at least 80% deuterated;
R 3 is hydrogen, a hydroxy protecting group, —C(O)R 7 , —C(O)OR 7 , or —C(O)NR 8a R 8b ;
R 1 is selected from the group consisting of:
1) —C(O)R 7 , —C(O)OR 7 , and —C(O)NR 8a R 8b ;
2) —P(O)(OR 7a )(OR 7b ); wherein R 7a and R 7b are each independently selected from the group consisting of a) hydrogen; b) unsubstituted or substituted —C 1 -C 8 alkyl;
3) —P(O)(OR 7a )—O—P(O)(OR 7b )(OR 7c ); wherein R 7a and R 7b are previously defined; R 7c is selected from the group consisting of a) hydrogen; b) unsubstituted or substituted —C 1 -C 8 alkyl;
4) —P(O)(OR 7a )—O—P(O)(OR 7b )—O—P(O)(OR 7c )(OR 7d ); wherein R 7a , R 7b and R 7c are previously defined; R 7d is selected from the group consisting of a) hydrogen; b) unsubstituted or substituted —C 1 -C 8 alkyl;
5)
where X is O or S; R 9 is R 7 ; R 10 , R 11 and R 12 are each independently selected from the group consisting of hydrogen; and unsubstituted or substituted —C 1 -C 8 alkyl; or R 11 is hydrogen, and R 12 and R 10 are taken together with the atoms to which they are attached to form a heterocyclic ring; or R 10 is hydrogen or unsubstituted or substituted —C 1 -C 8 alkyl and R 11 and R 12 are taken together with the carbon atom to which they are attached to form a ring; and R 13 is hydrogen or R 7 and
6)
where X is O or S; n is 1-4; R 14 is hydrogen or —(CO)—R 7 ;
Or, R1 and R 3 are taken together to form
where X is O or S; and R 15 is selected from the group consisting of a) hydrogen; b) unsubstituted or substituted —C 1 -C 8 alkyl; c) substituted or unsubstituted —C 2 -C 8 alkenyl; d) substituted or unsubstituted —C 2 -C 8 alkynyl; e) substituted or unsubstituted aryl; and f) substituted or unsubstituted heteroaryl;
R 2 a at each occurrence is selected from the group consisting of:
1) hydrogen;
2) halogen;
3) Substituted or unsubstituted —C 1 -C 8 alkyl;
4) Substituted or unsubstituted —C 2 -C 8 alkenyl; and
5) Substituted or unsubstituted —C 2 -C 8 alkynyl;
R 2b and R 4 are independently selected from the group consisting of:
1) hydrogen;
2) halogen;
3) —CN;
4) —N 3 ; and
5) OR 9 ;
R 7 at each occurrence is independently selected from the group consisting of: substituted or unsubstituted —C 1 -C 8 alkyl, substituted or unsubstituted —C 2 -C 8 alkenyl, substituted or unsubstituted —C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclic;
R 8a and R 8b at each occurrence are independently selected from the group consisting of:
hydrogen and R 7 ; or alternatively R 8a and R 8b taken together with the nitrogen atom to which they are attached form a heterocyclic ring;
R 9 at each occurrence is selected from the group consisting of: hydrogen, hydroxy protecting group, R 10a , —C(O)R 10a , —C(O)OR 10a , and —C(O)NR 11a R 11b ; wherein R 10a at each occurrence is independently selected from the group consisting of: substituted or unsubstituted —C 1 -C 8 alkyl, substituted or unsubstituted —C 2 -C 8 alkenyl, substituted or unsubstituted —C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclic; R 11a and R 11b at each occurrence are each independently selected from the group consisting of: hydrogen and R 10a ; or alternatively R 11a and R 11b taken together with the nitrogen atom to which they are attached form a heterocyclic ring;
R 5a and R 5b are independently selected from the group consisting of:
1) hydrogen;
2) substituted or unsubstituted —C 1 -C 8 alkyl;
3) substituted or unsubstituted —C 2 -C 8 alkenyl; and
4) substituted or unsubstituted —C 2 -C 8 alkynyl;
or R 5 a and R 5 b are taken together with the carbon atom to which they are attached to form a group selected from —C 3 -C 8 cycloalkyl, —C 3 -C 8 cycloalkenyl, or —C 3 -C 8 cycloalkynyl.
2. A compound of claim 1 represented by Formula III or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein R 2a , R 2b , R 4 , R 5a , R 5b , and R 7 are as previously defined.
3. A compound of claim 1 represented by Formula IV or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein X, R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , R 9 , R 10 , R 11 , R 12 , and R 13 are as previously defined.
4. A compound of claim 1 represented by Formula V or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein n, X, R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , R 8a , R 8b , and R 14 are as previously defined.
5. A compound of claim 1 represented by Formula VI or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein X, R 2a , R 2b , R 5a , R 5b , and R 15 are as previously defined.
6. A compound selected from
(a) compounds represented by Formula VII wherein, R 2a , R 2b , R 9 , R 11 , R 12 , and R 13 are delineated for each compound in Table 1:
TABLE 1
Example
R 2a
R 2b
R 9
R 11
R 12
R 13
1
Me
OH
Ph
Me
H
iPr
2
Me
OH
Ph
Me
H
Me
3
Me
OH
Ph
Me
H
Et
4
Me
OH
Ph
Me
H
Bn
5
Me
OH
Ph
Me
H
CH 2 CH(CH 3 ) 2
6
Me
F
Ph
Me
H
iPr
7
Me
F
Ph
Me
H
Me
8
Me
F
Ph
Me
H
Et
9
Me
F
Ph
Me
H
Bn
10
Me
F
Ph
Me
H
CH 2 CH(CH 3 ) 2
11
Me
OH
Ph
H
H
iPr
12
Me
OH
Ph
H
H
Me
13
Me
OH
Ph
H
H
Et
14
Me
OH
Ph
H
H
Bn
15
Me
OH
Ph
H
H
CH 2 CH(CH 3 ) 2
16
Me
F
Ph
H
H
iPr
17
Me
F
Ph
H
H
Me
18
Me
F
Ph
H
H
Et
19
Me
F
Ph
H
H
Bn
20
Me
F
Ph
H
H
CH 2 CH(CH 3 ) 2
21
Me
OH
Ph
iPr
H
iPr
22
Me
OH
Ph
iPr
H
Me
23
Me
OH
Ph
iPr
H
Et
24
Me
OH
Ph
iPr
H
Bn
25
Me
OH
Ph
iPr
H
CH 2 CH(CH 3 ) 2
26
Me
F
Ph
iPr
H
iPr
27
Me
F
Ph
iPr
H
Me
28
Me
F
Ph
iPr
H
Et
29
Me
F
Ph
iPr
H
Bn
30
Me
F
Ph
iPr
H
CH 2 CH(CH 3 ) 2
31
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
iPr
32
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Me
33
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Et
34
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Bn
35
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
36
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
iPr
37
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Me
38
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Et
39
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Bn
40
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
41
Me
OH
Ph
CH 2 Ph
H
iPr
42
Me
OH
Ph
CH 2 Ph
H
Me
43
Me
OH
Ph
CH 2 Ph
H
Et
44
Me
OH
Ph
CH 2 Ph
H
Bn
45
Me
OH
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
46
Me
F
Ph
CH 2 Ph
H
iPr
47
Me
F
Ph
CH 2 Ph
H
Me
48
Me
F
Ph
CH 2 Ph
H
Et
49
Me
F
Ph
CH 2 Ph
H
Bn
50
Me
F
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
51
Me
OH
1-Naphthyl
Me
H
iPr
52
Me
OH
1-Naphthyl
Me
H
Me
53
Me
OH
1-Naphthyl
Me
H
Et
54
Me
OH
1-Naphthyl
Me
H
Bn
55
Me
OH
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
56
Me
F
1-Naphthyl
Me
H
iPr
57
Me
F
1-Naphthyl
Me
H
Me
58
Me
F
1-Naphthyl
Me
H
Et
59
Me
F
1-Naphthyl
Me
H
Bn
60
Me
F
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
61
Me
OH
1-Naphthyl
H
H
iPr
62
Me
OH
1-Naphthyl
H
H
Me
63
Me
OH
1-Naphthyl
H
H
Et
64
Me
OH
1-Naphthyl
H
H
Bn
65
Me
OH
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
66
Me
F
1-Naphthyl
H
H
iPr
67
Me
F
1-Naphthyl
H
H
Me
68
Me
F
1-Naphthyl
H
H
Et
69
Me
F
1-Naphthyl
H
H
Bn
70
Me
F
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
71
Me
OH
1-Naphthyl
iPr
H
iPr
72
Me
OH
1-Naphthyl
iPr
H
Me
73
Me
OH
1-Naphthyl
iPr
H
Et
74
Me
OH
1-Naphthyl
iPr
H
Bn
75
Me
OH
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
76
Me
F
1-Naphthyl
iPr
H
iPr
77
Me
F
1-Naphthyl
iPr
H
Me
78
Me
F
1-Naphthyl
iPr
H
Et
79
Me
F
1-Naphthyl
iPr
H
Bn
80
Me
F
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
81
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
82
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
83
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
84
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
85
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
86
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
87
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
88
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
89
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
90
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
91
Me
OH
1-Naphthyl
CH 2 Ph
H
iPr
92
Me
OH
1-Naphthyl
CH 2 Ph
H
Me
93
Me
OH
1-Naphthyl
CH 2 Ph
H
Et
94
Me
OH
1-Naphthyl
CH 2 Ph
H
Bn
95
Me
OH
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
96
Me
F
1-Naphthyl
CH 2 Ph
H
iPr
97
Me
F
1-Naphthyl
CH 2 Ph
H
Me
98
Me
F
1-Naphthyl
CH 2 Ph
H
Et
99
Me
F
1-Naphthyl
CH 2 Ph
H
Bn
100
Me
F
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
101
Me
OH
p-F-Phenyl
Me
H
iPr
102
Me
OH
p-F-Phenyl
Me
H
Me
103
Me
OH
p-F-Phenyl
Me
H
Et
104
Me
OH
p-F-Phenyl
Me
H
Bn
105
Me
OH
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
106
Me
F
p-F-Phenyl
Me
H
iPr
107
Me
F
p-F-Phenyl
Me
H
Me
108
Me
F
p-F-Phenyl
Me
H
Et
109
Me
F
p-F-Phenyl
Me
H
Bn
110
Me
F
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
111
Me
OH
p-F-Phenyl
H
H
iPr
112
Me
OH
p-F-Phenyl
H
H
Me
113
Me
OH
p-F-Phenyl
H
H
Et
114
Me
OH
p-F-Phenyl
H
H
Bn
115
Me
OH
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
116
Me
F
p-F-Phenyl
H
H
iPr
117
Me
F
p-F-Phenyl
H
H
Me
118
Me
F
p-F-Phenyl
H
H
Et
119
Me
F
p-F-Phenyl
H
H
Bn
120
Me
F
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
121
Me
OH
p-F-Phenyl
iPr
H
iPr
122
Me
OH
p-F-Phenyl
iPr
H
Me
123
Me
OH
p-F-Phenyl
iPr
H
Et
124
Me
OH
p-F-Phenyl
iPr
H
Bn
125
Me
OH
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
126
Me
F
p-F-Phenyl
iPr
H
iPr
127
Me
F
p-F-Phenyl
iPr
H
Me
128
Me
F
p-F-Phenyl
iPr
H
Et
129
Me
F
p-F-Phenyl
iPr
H
Bn
130
Me
F
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
131
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
132
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
133
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
134
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
135
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
136
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
137
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
138
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
139
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
140
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
141
Me
OH
p-F-Phenyl
CH 2 Ph
H
iPr
142
Me
OH
p-F-Phenyl
CH 2 Ph
H
Me
143
Me
OH
p-F-Phenyl
CH 2 Ph
H
Et
144
Me
OH
p-F-Phenyl
CH 2 Ph
H
Bn
145
Me
OH
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
146
Me
F
p-F-Phenyl
CH 2 Ph
H
iPr
147
Me
F
p-F-Phenyl
CH 2 Ph
H
Me
148
Me
F
p-F-Phenyl
CH 2 Ph
H
Et
149
Me
F
p-F-Phenyl
CH 2 Ph
H
Bn
150
Me
F
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
151
Me
OH
iPr
Me
H
iPr
152
Me
OH
iPr
Me
H
Me
153
Me
OH
iPr
Me
H
Et
154
Me
OH
iPr
Me
H
Bn
155
Me
OH
iPr
Me
H
CH 2 CH(CH 3 ) 2
156
Me
F
iPr
Me
H
iPr
157
Me
F
iPr
Me
H
Me
158
Me
F
iPr
Me
H
Et
159
Me
F
iPr
Me
H
Bn
160
Me
F
iPr
Me
H
CH 2 CH(CH 3 ) 2
161
Me
OH
iPr
H
H
iPr
162
Me
OH
iPr
H
H
Me
163
Me
OH
iPr
H
H
Et
164
Me
OH
iPr
H
H
Bn
165
Me
OH
iPr
H
H
CH 2 CH(CH 3 ) 2
166
Me
F
iPr
H
H
iPr
167
Me
F
iPr
H
H
Me
168
Me
F
iPr
H
H
Et
169
Me
F
iPr
H
H
Bn
170
Me
F
iPr
H
H
CH 2 CH(CH 3 ) 2
171
Me
OH
iPr
iPr
H
iPr
172
Me
OH
iPr
iPr
H
Me
173
Me
OH
iPr
iPr
H
Et
174
Me
OH
iPr
iPr
H
Bn
175
Me
OH
iPr
iPr
H
CH 2 CH(CH 3 ) 2
176
Me
F
iPr
iPr
H
iPr
177
Me
F
iPr
iPr
H
Me
178
Me
F
iPr
iPr
H
Et
179
Me
F
iPr
iPr
H
Bn
180
Me
F
iPr
iPr
H
CH 2 CH(CH 3 ) 2
181
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
iPr
182
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Me
183
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Et
184
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Bn
185
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
186
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
iPr
187
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Me
188
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Et
189
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Bn
190
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
191
Me
OH
iPr
CH 2 Ph
H
iPr
192
Me
OH
iPr
CH 2 Ph
H
Me
193
Me
OH
iPr
CH 2 Ph
H
Et
194
Me
OH
iPr
CH 2 Ph
H
Bn
195
Me
OH
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
196
Me
F
iPr
CH 2 Ph
H
iPr
197
Me
F
iPr
CH 2 Ph
H
Me
198
Me
F
iPr
CH 2 Ph
H
Et
199
Me
F
iPr
CH 2 Ph
H
Bn
200
Me
F
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
(b) compounds represented by Formula VIII, wherein, R 2a , R 2b , R 9 , R 11 , R 12 , and R 13 are delineated for each compound in Table 2:
TABLE 2
Example
R 2a
R 2b
R 9
R 11
R 12
R 13
201
Me
OH
Ph
Me
H
iPr
202
Me
OH
Ph
Me
H
Me
203
Me
OH
Ph
Me
H
Et
204
Me
OH
Ph
Me
H
Bn
205
Me
OH
Ph
Me
H
CH 2 CH(CH 3 ) 2
206
Me
F
Ph
Me
H
iPr
207
Me
F
Ph
Me
H
Me
208
Me
F
Ph
Me
H
Et
209
Me
F
Ph
Me
H
Bn
210
Me
F
Ph
Me
H
CH 2 CH(CH 3 ) 2
211
Me
OH
Ph
H
H
iPr
212
Me
OH
Ph
H
H
Me
213
Me
OH
Ph
H
H
Et
214
Me
OH
Ph
H
H
Bn
215
Me
OH
Ph
H
H
CH 2 CH(CH 3 ) 2
216
Me
F
Ph
H
H
iPr
217
Me
F
Ph
H
H
Me
218
Me
F
Ph
H
H
Et
219
Me
F
Ph
H
H
Bn
220
Me
F
Ph
H
H
CH 2 CH(CH 3 ) 2
221
Me
OH
Ph
iPr
H
iPr
222
Me
OH
Ph
iPr
H
Me
223
Me
OH
Ph
iPr
H
Et
224
Me
OH
Ph
iPr
H
Bn
225
Me
OH
Ph
iPr
H
CH 2 CH(CH 3 ) 2
226
Me
F
Ph
iPr
H
iPr
227
Me
F
Ph
iPr
H
Me
228
Me
F
Ph
iPr
H
Et
229
Me
F
Ph
iPr
H
Bn
230
Me
F
Ph
iPr
H
CH 2 CH(CH 3 ) 2
231
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
iPr
232
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Me
233
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Et
234
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Bn
235
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
236
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
iPr
237
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Me
238
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Et
239
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Bn
240
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
241
Me
OH
Ph
CH 2 Ph
H
iPr
242
Me
OH
Ph
CH 2 Ph
H
Me
243
Me
OH
Ph
CH 2 Ph
H
Et
244
Me
OH
Ph
CH 2 Ph
H
Bn
245
Me
OH
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
246
Me
F
Ph
CH 2 Ph
H
iPr
247
Me
F
Ph
CH 2 Ph
H
Me
248
Me
F
Ph
CH 2 Ph
H
Et
249
Me
F
Ph
CH 2 Ph
H
Bn
250
Me
F
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
251
Me
OH
1-Naphthyl
Me
H
iPr
252
Me
OH
1-Naphthyl
Me
H
Me
253
Me
OH
1-Naphthyl
Me
H
Et
254
Me
OH
1-Naphthyl
Me
H
Bn
255
Me
OH
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
256
Me
F
1-Naphthyl
Me
H
iPr
257
Me
F
1-Naphthyl
Me
H
Me
258
Me
F
1-Naphthyl
Me
H
Et
259
Me
F
1-Naphthyl
Me
H
Bn
260
Me
F
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
261
Me
OH
1-Naphthyl
H
H
iPr
262
Me
OH
1-Naphthyl
H
H
Me
263
Me
OH
1-Naphthyl
H
H
Et
264
Me
OH
1-Naphthyl
H
H
Bn
265
Me
OH
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
266
Me
F
1-Naphthyl
H
H
iPr
267
Me
F
1-Naphthyl
H
H
Me
268
Me
F
1-Naphthyl
H
H
Et
269
Me
F
1-Naphthyl
H
H
Bn
270
Me
F
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
271
Me
OH
1-Naphthyl
iPr
H
iPr
272
Me
OH
1-Naphthyl
iPr
H
Me
273
Me
OH
1-Naphthyl
iPr
H
Et
274
Me
OH
1-Naphthyl
iPr
H
Bn
275
Me
OH
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
276
Me
F
1-Naphthyl
iPr
H
iPr
277
Me
F
1-Naphthyl
iPr
H
Me
278
Me
F
1-Naphthyl
iPr
H
Et
279
Me
F
1-Naphthyl
iPr
H
Bn
280
Me
F
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
281
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
282
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
283
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
284
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
285
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
286
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
287
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
288
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
289
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
290
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
291
Me
OH
1-Naphthyl
CH 2 Ph
H
iPr
292
Me
OH
1-Naphthyl
CH 2 Ph
H
Me
293
Me
OH
1-Naphthyl
CH 2 Ph
H
Et
294
Me
OH
1-Naphthyl
CH 2 Ph
H
Bn
295
Me
OH
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
296
Me
F
1-Naphthyl
CH 2 Ph
H
iPr
297
Me
F
1-Naphthyl
CH 2 Ph
H
Me
298
Me
F
1-Naphthyl
CH 2 Ph
H
Et
299
Me
F
1-Naphthyl
CH 2 Ph
H
Bn
300
Me
F
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
301
Me
OH
p-F-Phenyl
Me
H
iPr
302
Me
OH
p-F-Phenyl
Me
H
Me
303
Me
OH
p-F-Phenyl
Me
H
Et
304
Me
OH
p-F-Phenyl
Me
H
Bn
305
Me
OH
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
306
Me
F
p-F-Phenyl
Me
H
iPr
307
Me
F
p-F-Phenyl
Me
H
Me
308
Me
F
p-F-Phenyl
Me
H
Et
309
Me
F
p-F-Phenyl
Me
H
Bn
310
Me
F
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
311
Me
OH
p-F-Phenyl
H
H
iPr
312
Me
OH
p-F-Phenyl
H
H
Me
313
Me
OH
p-F-Phenyl
H
H
Et
314
Me
OH
p-F-Phenyl
H
H
Bn
315
Me
OH
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
316
Me
F
p-F-Phenyl
H
H
iPr
317
Me
F
p-F-Phenyl
H
H
Me
318
Me
F
p-F-Phenyl
H
H
Et
319
Me
F
p-F-Phenyl
H
H
Bn
320
Me
F
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
321
Me
OH
p-F-Phenyl
iPr
H
iPr
322
Me
OH
p-F-Phenyl
iPr
H
Me
323
Me
OH
p-F-Phenyl
iPr
H
Et
324
Me
OH
p-F-Phenyl
iPr
H
Bn
325
Me
OH
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
326
Me
F
p-F-Phenyl
iPr
H
iPr
327
Me
F
p-F-Phenyl
iPr
H
Me
328
Me
F
p-F-Phenyl
iPr
H
Et
329
Me
F
p-F-Phenyl
iPr
H
Bn
330
Me
F
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
331
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
332
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
333
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
334
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
335
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
336
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
337
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
338
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
339
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
340
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
341
Me
OH
p-F-Phenyl
CH 2 Ph
H
iPr
342
Me
OH
p-F-Phenyl
CH 2 Ph
H
Me
343
Me
OH
p-F-Phenyl
CH 2 Ph
H
Et
344
Me
OH
p-F-Phenyl
CH 2 Ph
H
Bn
345
Me
OH
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
346
Me
F
p-F-Phenyl
CH 2 Ph
H
iPr
347
Me
F
p-F-Phenyl
CH 2 Ph
H
Me
348
Me
F
p-F-Phenyl
CH 2 Ph
H
Et
349
Me
F
p-F-Phenyl
CH 2 Ph
H
Bn
350
Me
F
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
351
Me
OH
iPr
Me
H
iPr
352
Me
OH
iPr
Me
H
Me
353
Me
OH
iPr
Me
H
Et
354
Me
OH
iPr
Me
H
Bn
355
Me
OH
iPr
Me
H
CH 2 CH(CH 3 ) 2
356
Me
F
iPr
Me
H
iPr
357
Me
F
iPr
Me
H
Me
358
Me
F
iPr
Me
H
Et
359
Me
F
iPr
Me
H
Bn
360
Me
F
iPr
Me
H
CH 2 CH(CH 3 ) 2
361
Me
OH
iPr
H
H
iPr
362
Me
OH
iPr
H
H
Me
363
Me
OH
iPr
H
H
Et
364
Me
OH
iPr
H
H
Bn
365
Me
OH
iPr
H
H
CH 2 CH(CH 3 ) 2
366
Me
F
iPr
H
H
iPr
367
Me
F
iPr
H
H
Me
368
Me
F
iPr
H
H
Et
369
Me
F
iPr
H
H
Bn
370
Me
F
iPr
H
H
CH 2 CH(CH 3 ) 2
371
Me
OH
iPr
iPr
H
iPr
372
Me
OH
iPr
iPr
H
Me
373
Me
OH
iPr
iPr
H
Et
374
Me
OH
iPr
iPr
H
Bn
375
Me
OH
iPr
iPr
H
CH 2 CH(CH 3 ) 2
376
Me
F
iPr
iPr
H
iPr
377
Me
F
iPr
iPr
H
Me
378
Me
F
iPr
iPr
H
Et
379
Me
F
iPr
iPr
H
Bn
380
Me
F
iPr
iPr
H
CH 2 CH(CH 3 ) 2
381
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
iPr
382
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Me
383
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Et
384
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Bn
385
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
386
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
iPr
387
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Me
388
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Et
389
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Bn
390
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
391
Me
OH
iPr
CH 2 Ph
H
iPr
392
Me
OH
iPr
CH 2 Ph
H
Me
393
Me
OH
iPr
CH 2 Ph
H
Et
194
Me
OH
iPr
CH 2 Ph
H
Bn
395
Me
OH
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
396
Me
F
iPr
CH 2 Ph
H
iPr
397
Me
F
iPr
CH 2 Ph
H
Me
398
Me
F
iPr
CH 2 Ph
H
Et
399
Me
F
iPr
CH 2 Ph
H
Bn
400
Me
F
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
(c) compounds represented by Formula IX, wherein, R 2a , R 2b , R 9 , R 11 , R 12 , and R 13 are delineated for each compound in Table 3:
TABLE 3
Example
R 2a
R 2b
R 9
R 11
R 12
R 13
401
Me
OH
Ph
Me
H
iPr
402
Me
OH
Ph
Me
H
Me
403
Me
OH
Ph
Me
H
Et
404
Me
OH
Ph
Me
H
Bn
405
Me
OH
Ph
Me
H
CH 2 CH(CH 3 ) 2
406
Me
F
Ph
Me
H
iPr
407
Me
F
Ph
Me
H
Me
408
Me
F
Ph
Me
H
Et
409
Me
F
Ph
Me
H
Bn
410
Me
F
Ph
Me
H
CH 2 CH(CH 3 ) 2
411
Me
OH
Ph
H
H
iPr
412
Me
OH
Ph
H
H
Me
413
Me
OH
Ph
H
H
Et
414
Me
OH
Ph
H
H
Bn
415
Me
OH
Ph
H
H
CH 2 CH(CH 3 ) 2
416
Me
F
Ph
H
H
iPr
417
Me
F
Ph
H
H
Me
418
Me
F
Ph
H
H
Et
419
Me
F
Ph
H
H
Bn
420
Me
F
Ph
H
H
CH 2 CH(CH 3 ) 2
421
Me
OH
Ph
iPr
H
iPr
422
Me
OH
Ph
iPr
H
Me
423
Me
OH
Ph
iPr
H
Et
424
Me
OH
Ph
iPr
H
Bn
425
Me
OH
Ph
iPr
H
CH 2 CH(CH 3 ) 2
426
Me
F
Ph
iPr
H
iPr
427
Me
F
Ph
iPr
H
Me
428
Me
F
Ph
iPr
H
Et
429
Me
F
Ph
iPr
H
Bn
430
Me
F
Ph
iPr
H
CH 2 CH(CH 3 ) 2
431
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
iPr
432
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Me
433
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Et
434
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
Bn
435
Me
OH
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
436
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
iPr
437
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Me
438
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Et
439
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
Bn
440
Me
F
Ph
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
441
Me
OH
Ph
CH 2 Ph
H
iPr
442
Me
OH
Ph
CH 2 Ph
H
Me
443
Me
OH
Ph
CH 2 Ph
H
Et
444
Me
OH
Ph
CH 2 Ph
H
Bn
445
Me
OH
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
446
Me
F
Ph
CH 2 Ph
H
iPr
447
Me
F
Ph
CH 2 Ph
H
Me
448
Me
F
Ph
CH 2 Ph
H
Et
449
Me
F
Ph
CH 2 Ph
H
Bn
450
Me
F
Ph
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
451
Me
OH
1-Naphthyl
Me
H
iPr
452
Me
OH
1-Naphthyl
Me
H
Me
453
Me
OH
1-Naphthyl
Me
H
Et
454
Me
OH
1-Naphthyl
Me
H
Bn
455
Me
OH
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
456
Me
F
1-Naphthyl
Me
H
iPr
457
Me
F
1-Naphthyl
Me
H
Me
458
Me
F
1-Naphthyl
Me
H
Et
459
Me
F
1-Naphthyl
Me
H
Bn
460
Me
F
1-Naphthyl
Me
H
CH 2 CH(CH 3 ) 2
461
Me
OH
1-Naphthyl
H
H
iPr
462
Me
OH
1-Naphthyl
H
H
Me
463
Me
OH
1-Naphthyl
H
H
Et
464
Me
OH
1-Naphthyl
H
H
Bn
465
Me
OH
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
466
Me
F
1-Naphthyl
H
H
iPr
467
Me
F
1-Naphthyl
H
H
Me
468
Me
F
1-Naphthyl
H
H
Et
469
Me
F
1-Naphthyl
H
H
Bn
470
Me
F
1-Naphthyl
H
H
CH 2 CH(CH 3 ) 2
471
Me
OH
1-Naphthyl
iPr
H
iPr
472
Me
OH
1-Naphthyl
iPr
H
Me
473
Me
OH
1-Naphthyl
iPr
H
Et
474
Me
OH
1-Naphthyl
iPr
H
Bn
475
Me
OH
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
476
Me
F
1-Naphthyl
iPr
H
iPr
477
Me
F
1-Naphthyl
iPr
H
Me
478
Me
F
1-Naphthyl
iPr
H
Et
479
Me
F
1-Naphthyl
iPr
H
Bn
480
Me
F
1-Naphthyl
iPr
H
CH 2 CH(CH 3 ) 2
481
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
482
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
483
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
484
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
485
Me
OH
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
486
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
iPr
487
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Me
488
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Et
489
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
Bn
490
Me
F
1-Naphthyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
491
Me
OH
1-Naphthyl
CH 2 Ph
H
iPr
492
Me
OH
1-Naphthyl
CH 2 Ph
H
Me
493
Me
OH
1-Naphthyl
CH 2 Ph
H
Et
494
Me
OH
1-Naphthyl
CH 2 Ph
H
Bn
495
Me
OH
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
496
Me
F
1-Naphthyl
CH 2 Ph
H
iPr
497
Me
F
1-Naphthyl
CH 2 Ph
H
Me
498
Me
F
1-Naphthyl
CH 2 Ph
H
Et
499
Me
F
1-Naphthyl
CH 2 Ph
H
Bn
500
Me
F
1-Naphthyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
501
Me
OH
p-F-Phenyl
Me
H
iPr
502
Me
OH
p-F-Phenyl
Me
H
Me
503
Me
OH
p-F-Phenyl
Me
H
Et
504
Me
OH
p-F-Phenyl
Me
H
Bn
505
Me
OH
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
506
Me
F
p-F-Phenyl
Me
H
iPr
507
Me
F
p-F-Phenyl
Me
H
Me
508
Me
F
p-F-Phenyl
Me
H
Et
509
Me
F
p-F-Phenyl
Me
H
Bn
510
Me
F
p-F-Phenyl
Me
H
CH 2 CH(CH 3 ) 2
511
Me
OH
p-F-Phenyl
H
H
iPr
512
Me
OH
p-F-Phenyl
H
H
Me
513
Me
OH
p-F-Phenyl
H
H
Et
514
Me
OH
p-F-Phenyl
H
H
Bn
515
Me
OH
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
516
Me
F
p-F-Phenyl
H
H
iPr
517
Me
F
p-F-Phenyl
H
H
Me
518
Me
F
p-F-Phenyl
H
H
Et
519
Me
F
p-F-Phenyl
H
H
Bn
520
Me
F
p-F-Phenyl
H
H
CH 2 CH(CH 3 ) 2
521
Me
OH
p-F-Phenyl
iPr
H
iPr
522
Me
OH
p-F-Phenyl
iPr
H
Me
523
Me
OH
p-F-Phenyl
iPr
H
Et
524
Me
OH
p-F-Phenyl
iPr
H
Bn
525
Me
OH
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
526
Me
F
p-F-Phenyl
iPr
H
iPr
527
Me
F
p-F-Phenyl
iPr
H
Me
528
Me
F
p-F-Phenyl
iPr
H
Et
529
Me
F
p-F-Phenyl
iPr
H
Bn
530
Me
F
p-F-Phenyl
iPr
H
CH 2 CH(CH 3 ) 2
531
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
532
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
533
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
534
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
535
Me
OH
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
536
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
iPr
537
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Me
538
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Et
539
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
Bn
540
Me
F
p-F-Phenyl
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
541
Me
OH
p-F-Phenyl
CH 2 Ph
H
iPr
542
Me
OH
p-F-Phenyl
CH 2 Ph
H
Me
543
Me
OH
p-F-Phenyl
CH 2 Ph
H
Et
544
Me
OH
p-F-Phenyl
CH 2 Ph
H
Bn
545
Me
OH
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
546
Me
F
p-F-Phenyl
CH 2 Ph
H
iPr
547
Me
F
p-F-Phenyl
CH 2 Ph
H
Me
548
Me
F
p-F-Phenyl
CH 2 Ph
H
Et
549
Me
F
p-F-Phenyl
CH 2 Ph
H
Bn
550
Me
F
p-F-Phenyl
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
551
Me
OH
iPr
Me
H
iPr
552
Me
OH
iPr
Me
H
Me
553
Me
OH
iPr
Me
H
Et
554
Me
OH
iPr
Me
H
Bn
555
Me
OH
iPr
Me
H
CH 2 CH(CH 3 ) 2
556
Me
F
iPr
Me
H
iPr
557
Me
F
iPr
Me
H
Me
558
Me
F
iPr
Me
H
Et
559
Me
F
iPr
Me
H
Bn
560
Me
F
iPr
Me
H
CH 2 CH(CH 3 ) 2
561
Me
OH
iPr
H
H
iPr
562
Me
OH
iPr
H
H
Me
563
Me
OH
iPr
H
H
Et
564
Me
OH
iPr
H
H
Bn
565
Me
OH
iPr
H
H
CH 2 CH(CH 3 ) 2
566
Me
F
iPr
H
H
iPr
567
Me
F
iPr
H
H
Me
568
Me
F
iPr
H
H
Et
569
Me
F
iPr
H
H
Bn
570
Me
F
iPr
H
H
CH 2 CH(CH 3 ) 2
571
Me
OH
iPr
iPr
H
iPr
572
Me
OH
iPr
iPr
H
Me
573
Me
OH
iPr
iPr
H
Et
574
Me
OH
iPr
iPr
H
Bn
575
Me
OH
iPr
iPr
H
CH 2 CH(CH 3 ) 2
576
Me
F
iPr
iPr
H
iPr
577
Me
F
iPr
iPr
H
Me
578
Me
F
iPr
iPr
H
Et
579
Me
F
iPr
iPr
H
Bn
580
Me
F
iPr
iPr
H
CH 2 CH(CH 3 ) 2
581
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
iPr
582
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Me
583
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Et
584
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
Bn
585
Me
OH
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
586
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
iPr
587
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Me
588
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Et
589
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
Bn
590
Me
F
iPr
CH 2 CH(CH 3 ) 2
H
CH 2 CH(CH 3 ) 2
591
Me
OH
iPr
CH 2 Ph
H
iPr
592
Me
OH
iPr
CH 2 Ph
H
Me
593
Me
OH
iPr
CH 2 Ph
H
Et
594
Me
OH
iPr
CH 2 Ph
H
Bn
595
Me
OH
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
596
Me
F
iPr
CH 2 Ph
H
iPr
597
Me
F
iPr
CH 2 Ph
H
Me
598
Me
F
iPr
CH 2 Ph
H
Et
599
Me
F
iPr
CH 2 Ph
H
Bn
600
Me
F
iPr
CH 2 Ph
H
CH 2 CH(CH 3 ) 2
and
(d) compounds represented by Formula X, wherein, R 2a , R 2b , R 5a , R 5b , R 8a , and R 8b are delineated for each compound in Table 4:
TABLE 4
Compound
R 2a
R 2b
601
Me
OH
PhCH 2 NH
602
Me
OH
PhCH 2 NH
603
Me
OH
PhCH 2 NH
604
Me
OH
i PrNH
605
Me
OH
i PrNH
606
Me
OH
i PrNH
607
Me
OH
t BuNH
608
Me
OH
t BuNH
609
Me
OH
t BuNH
610
Me
OH
611
Me
OH
612
Me
OH
613
Me
OH
614
Me
OH
615
Me
OH
616
Me
OH
617
Me
OH
618
Me
OH
619
Me
OH
NHCH 2 CO 2 Et
620
Me
OH
NH CH 2 CO 2 Et
621
Me
OH
NH CH 2 CO 2 Et
622
Me
OH
NH CH 2 CO 2 t Bu
623
Me
OH
NH CH 2 CO 2 t Bu
624
Me
OH
NH CH 2 CO 2 t Bu
625
Me
OH
NH CH 2 CO 2 H
626
Me
OH
NH CH 2 CO 2 H
627
Me
OH
NH CH 2 CO 2 H
628
Me
OH
NH CH 2 CH 2 NMe 2
629
Me
OH
NH CH 2 CH 2 NMe 2
630
Me
OH
NH CH 2 CH 2 NMe 2
631
Me
F
PhCH 2 NH
632
Me
F
PhCH 2 NH
633
Me
F
PhCH 2 NH
634
Me
F
i PrNH
635
Me
F
i PrNH
636
Me
F
i PrNH
637
Me
F
t BuNH
638
Me
F
t BuNH
639
Me
F
t BuNH
640
Me
F
641
Me
F
642
Me
F
643
Me
F
644
Me
F
645
Me
F
646
Me
F
647
Me
F
648
Me
F
649
Me
F
NHCH 2 CO 2 Et
650
Me
F
NH CH 2 CO 2 Et
651
Me
F
NH CH 2 CO 2 Et
652
Me
F
NH CH 2 CO 2 t Bu
653
Me
F
NH CH 2 CO 2 t Bu
654
Me
F
NH CH 2 CO 2 t Bu
655
Me
F
NH CH 2 CO 2 H
656
Me
F
NH CH 2 CO 2 H
657
Me
F
NH CH 2 CO 2 H
658
Me
F
NH CH 2 CH 2 NMe 2
659
Me
F
NH CH 2 CH 2 NMe 2
660
Me
F
NH CH 2 CH 2 NMe 2
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein R 2a is C 1 -C 6 -alkyl; CF 3 , or F.
8. The compound of claim 1 , wherein R 2a is methyl.
9. The compound of claim 1 , wherein:
R 2a is C 1 -C 6 -alkyl, CF 3 , or F;
R 2b is hydrogen, halogen, —CN, —N 3 or OH;
R 4 is hydrogen, halogen or OH;
R 5a and R 5b are independently hydrogen or C 1 -C 6 -alkyl or R 5a and R 5b , together with the carbon atom to which they are attached, form a C 3 -C 6 -cycloalkyl group;
R 9 is aryl, substituted aryl or C 1 -C 6 -alkyl;
R 11 is hydrogen, C 1 -C 6 -alkyl or aryl-C 1 -C 3 -alkyl;
R 12 is hydrogen; and
R 13 is hydrogen, C 1 -C 6 -alkyl or aryl-C 1 -C 3 -alkyl.
10. The compound of claim 9 , wherein:
R 2a is methyl, CF 3 or F;
R 2b is F or OH;
R 4 is hydrogen;
one of R 5a and R 5b is methyl and the other is hydrogen; or R 5a and R 5b are both hydrogen; or R 5a and R 5b , together with the carbon atom to which they are attached, form a cyclopropyl group;
R 9 is phenyl, naphthyl, p-fluorophenyl or isopropyl;
R 11 is hydrogen, methyl, isopropyl, isobutyl or benzyl;
R 12 is hydrogen; and
R 13 is hydrogen, methyl, isopropyl, isobutyl or benzyl.
11. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier or excipient.
12. The pharmaceutical composition of claim 11 , further comprising another anti-HCV agent.
13. The pharmaceutical composition of claim 11 , further comprising an agent selected from interferon, ribavirin, amantadine, another HCV protease inhibitor, an HCV polymerase inhibitor, an HCV helicase inhibitor, or an internal ribosome entry site inhibitor.
14. The pharmaceutical composition of claim 11 , further comprising pegylated interferon.
15. A method of treating a viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
16. The method according to claim 15 , wherein the viral infection is hepatitis C virus.
17. The method of claim 16 , further comprising administering concurrently an additional anti-hepatitis C virus agent.
18. The method of claim 17 , wherein said additional anti-hepatitis C virus agent is selected from the group consisting of α-interferon, β-interferon, ribavirin, and amantadine.
19. The method of claim 17 , wherein said additional anti-hepatitis C virus agent is an inhibitor of hepatitis C virus helicase, polymerase, metalloprotease, or IRES.