US2018079774A1PendingUtilityA1
Substituted nucleosides, nucleotides and analogs thereof
Est. expiryJun 26, 2033(~6.9 yrs left)· nominal 20-yr term from priority
A61P 31/14A61P 31/12C07H 19/20C07H 19/16C07H 19/06C07H 19/10C07H 19/11
46
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.
Claims
exact text as granted — not AI-modified1 . A method for ameliorating, treating or preventing a norovirus infection comprising contacting a cell infected with the norovirus with an effective amount of a compound of Formula (II) or Formula (III), or a pharmaceutically acceptable salt of the foregoing, wherein Formula (II) and Formula (III) are:
wherein:
B 1B and B 1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group;
R 1B is selected from the group consisting of O − , OH, an optionally substituted C 1-6 alkoxy,
an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative;
R 1C and R 2C are independently selected from the group consisting of O − , OH, an optionally substituted C 1-6 alkoxy,
an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or
R 1C is
and R 2C is O − or OH;
R 2B and R 3C are independently selected from the group consisting of halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl, an optionally substituted C 2-6 alkynyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted —O—C 1-6 alkyl, an optionally substituted —O—C 3-6 alkenyl, an optionally substituted —O—C 3-6 alkynyl and cyano;
R 4C is selected from the group consisting of OH, —OC(═O)R″ C and an optionally substituted O-linked amino acid;
R 3B and R 5C are independently selected from the group consisting of hydrogen, halogen, OR 1D , an optionally substituted O-linked amino acid, azido and NR 2D R 3D ;
R 1D is hydrogen or —C(═O)R″ D ;
R 2D and R 3D are independently hydrogen or an optionally substituted C 1-6 alkyl;
R 4B and R 6C are independently selected from the group consisting of hydrogen, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
R 5B , R 6B , R 8B , R 9B , R 9C , R 10C , R 12C and R 13C are independently selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl and an optionally substituted aryl;
R 7B , R 10B , R 11C and R 14C are independently selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl, an optionally substituted aryl, an optionally substituted —O—C 1-24 alkyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl, an optionally substituted —O-monocyclic heterocyclyl and
R 11B1 , R 11B2 , R 15C1 and R 15C2 are independently selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl and an optionally substituted aryl;
R 16C , R 17C and R 18C are independently absent or hydrogen;
for Formula (III), is a single bond or a double bond;
when is a single bond, each R 7C and each R 8C is independently hydrogen or halogen; and
when is a double bond, each R 7C is absent and each R 8C is independently hydrogen or halogen;
R″ C and R″ D are independently an optionally substituted C 1-24 -alkyl;
d and j are independently 1 or 2;
e1 and k1 are independently 0 or 1;
e2 and k2 are independently 3, 4 or 5;
n is 0 or 1;
Z 1B , Z 2B and Z 1C are independently O or S.
2 . (canceled)
3 . (canceled)
4 . (canceled)
5 . (canceled)
6 . (canceled)
7 . (canceled)
8 . (canceled)
9 . (canceled)
10 . (canceled)
11 . (canceled)
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . (canceled)
16 . (canceled)
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . (canceled)
22 . (canceled)
23 . (canceled)
24 . (canceled)
25 . (canceled)
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . (canceled)
36 . (canceled)
37 . (canceled)
38 . (canceled)
39 . (canceled)
40 . (canceled)
41 . (canceled)
42 . (canceled)
43 . (canceled)
44 . (canceled)
45 . (canceled)
46 . (canceled)
47 . (canceled)
48 . (canceled)
49 . (canceled)
50 . (canceled)
51 . (canceled)
52 . (canceled)
53 . (canceled)
54 . (canceled)
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 . (canceled)
106 . (canceled)
107 . (canceled)
108 . (canceled)
109 . (canceled)
110 . (canceled)
111 . (canceled)
112 . (canceled)
113 . (canceled)
114 . (canceled)
115 . The method of claim 1 , wherein the compound is a compound of Formula (II).
116 . The method of claim 115 , wherein R 1B is O − or OH.
117 . The method of claim 115 , wherein R 1B is an optionally substituted C 1-6 alkoxy,
118 . (canceled)
119 . (canceled)
120 . (canceled)
121 . (canceled)
122 . The method of claim 115 , wherein R 1B is an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.
123 . The method of claim 115 , wherein R 1B is selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine and ester derivatives thereof.
124 . The method of claim 115 , wherein R 1B is selected from the group consisting of alanine isopropyl ester, alanine cyclohexyl ester, alanine neopentyl ester, valine isopropyl ester and leucine isopropyl ester.
125 . The method of claim 115 , wherein R 1B has the structure
wherein R 12B is selected from the group consisting of hydrogen, an optionally substituted C 1-6 -alkyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted aryl(C 1-6 alkyl) and an optionally substituted haloalkyl; R 13B is selected from the group consisting of hydrogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 haloalkyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted C 6 aryl, an optionally substituted C 10 aryl and an optionally substituted aryl(C 1-6 alkyl); and R 14B is hydrogen or an optionally substituted C 1-4 -alkyl; or R 13B and R 14B are taken together to form an optionally substituted C 3-6 cycloalkyl.
126 . (canceled)
127 . (canceled)
128 . (canceled)
129 . (canceled)
130 . (canceled)
131 . (canceled)
132 . (canceled)
133 . (canceled)
134 . (canceled)
135 . (canceled)
136 . (canceled)
137 . (canceled)
138 . The method of claim 115 , wherein R 2B is unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted —O—C 1-6 alkyl, unsubstituted —O—C 3-6 alkenyl or unsubstituted —O—C 3-6 alkynyl.
139 . The method of claim 115 , wherein R 2B is cyano.
140 . The method of claim 115 , wherein R 4B is hydrogen.
141 . The method of claim 115 , wherein R 4B is halogen.
142 . (canceled)
143 . (canceled)
144 . (canceled)
145 . (canceled)
146 . The method of claim 115 , wherein R 3B is hydrogen, halogen, OR 1D , OH, or —OC(═O)R″ D .
147 . (canceled)
148 . (canceled)
149 . (canceled)
150 . (canceled)
151 . (canceled)
152 . The method of claim 115 , wherein R 3B is an optionally substituted O-linked amino acid, azido, NR 2D R 3D , or NH 2 .
153 . (canceled)
154 . (canceled)
155 . (canceled)
156 . (canceled)
157 . (canceled)
158 . The method of claim 115 , wherein Z 1B is O.
159 . (canceled)
160 . The method of claim 115 , wherein B 1B is selected from the group consisting of:
wherein:
R AB2 is selected from the group consisting of hydrogen, halogen and NHR JB2 , wherein R JB2 is selected from the group consisting of hydrogen, —C(═O)R KB2 and —C(═O)OR LB2 ;
R BB2 is halogen or NHR WB2 , wherein R WB2 is selected from the group consisting of hydrogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl, an optionally substituted C 3-8 cycloalkyl, —C(═O)R MB2 and —C(═O)OR NB2 ;
R CB2 is hydrogen or NHR OB2 , wherein R OB2 is selected from the group consisting of hydrogen, —C(═O)R PB2 and —C(═O)OR QB2 ;
R DB2 is selected from the group consisting of hydrogen, deuterium, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
R EB2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted C 1-6 alkyl, an optionally substituted C 3-8 cycloalkyl, —C(═O)R RB2 and —C(═O)OR SB2 ;
R FB2 is selected from the group consisting of hydrogen, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
Y 2B and Y 3B are independently N or CR IB2 , wherein R B2 is selected from the group consisting of hydrogen, halogen, an optionally substituted C 1-6 -alkyl, an optionally substituted C 2-6 -alkenyl and an optionally substituted C 2-6 -alkynyl;
R GB2 is an optionally substituted C 1-6 alkyl;
R HB2 is hydrogen or NHR TB2 , wherein R TB2 is independently selected from the group consisting of hydrogen, —C(═O)R UB2 and —C(═O)OR VB2 ; and
R KB2 , R LB2 , R MB2 , R NB2 , R PB2 , R QB2 R RB2 , R SB2 , R UB2 and R VB2 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 6-10 aryl, heteroaryl, heteroalicyclyl, aryl(C 1-6 alkyl), heteroaryl(C 1-6 alkyl) and heteroalicyclyl(C 1-6 alkyl).
161 . (canceled)
162 . (canceled)
163 . (canceled)
164 . (canceled)
165 . (canceled)
166 . (canceled)
167 . The method of claim 1 , wherein the compound is a compound of Formula (III).
168 . (canceled)
169 . (canceled)
170 . (canceled)
171 . (canceled)
172 . (canceled)
173 . (canceled)
174 . (canceled)
175 . (canceled)
176 . (canceled)
177 . (canceled)
178 . (canceled)
179 . (canceled)
180 . (canceled)
181 . (canceled)
182 . (canceled)
183 . (canceled)
184 . (canceled)
185 . (canceled)
186 . (canceled)
187 . (canceled)
188 . (canceled)
189 . (canceled)
190 . (canceled)
191 . (canceled)
192 . (canceled)
193 . (canceled)
194 . (canceled)
195 . (canceled)
196 . (canceled)
197 . (canceled)
198 . (canceled)
199 . (canceled)
200 . (canceled)
201 . (canceled)
202 . (canceled)
203 . (canceled)
204 . (canceled)
205 . (canceled)
206 . (canceled)
207 . (canceled)
208 . (canceled)
209 . (canceled)
210 . (canceled)
211 . (canceled)
212 . (canceled)
213 . (canceled)
214 . (canceled)
215 . (canceled)
216 . (canceled)
217 . (canceled)
218 . (canceled)
219 . (canceled)
220 . (canceled)
221 . (canceled)
222 . (canceled)
223 . (canceled)
224 . (canceled)
225 . (canceled)
226 . (canceled)
227 . (canceled)
228 . (canceled)
229 . (canceled)
230 . (canceled)
231 . (canceled)
232 . (canceled)
233 . (canceled)
234 . (canceled)
235 . (canceled)
236 . The method of claim 115 , wherein the compound of Formula (II) is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
237 . The method of claim 115 , wherein the compound of Formula (II) is selected from the group consisting of:
or a pharmaceutically acceptable salt of the foregoing.
238 . (canceled)
239 . (canceled)
240 . (canceled)
241 . (canceled)
242 . (canceled)
243 . (canceled)
244 . (canceled)Join the waitlist — get patent alerts
Track US2018079774A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.