US2003199521A1PendingUtilityA1
Compounds, methods and compositions useful for the treatment of bovine viral diarrhea virus (BVDV) infection and hepatitis C virus (HCV) infection
Priority: Jan 13, 2001Filed: Jan 11, 2002Published: Oct 23, 2003
Est. expiryJan 13, 2021(expired)· nominal 20-yr term from priority
Inventors:Christine C. DykstraMaurice GivensDavid StringfellowKenny BrockDavid W. BoykinArvind KumarW. David WilsonRichard R. TidwellChad Stephens
A61P 31/12C07D 307/52C07D 307/54C07D 405/04C07D 277/28A61K 31/401C07D 405/14C07D 333/20A61K 31/381C07D 207/09A61K 31/341A61P 1/12A61K 31/426A61K 31/4178A61K 31/4184C07D 405/10C07D 307/14C07D 207/08
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Claims
Abstract
The present invention relates to novel compounds and methods that are useful in treating members of the Flaviviridae family of viruses. Compounds of the present invention will have a structure according to Formulas (I)-(VI) as recited throughout the application.
Claims
exact text as granted — not AI-modifiedThat which is claimed is:
1 . A compound according to Formula I:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
2 . The compound according to claim 1 , wherein:
X 1 is O; X 2 is C; X 3 is NH X 4 is N and R 2 , R 3 and R 4 are each H.
3 . The compound according to claim 1 , wherein A is
and R 6 is alkyl.
4 . The compound according to claim 1 , wherein A is
and R 7 and R 8 are each H.
5 . The compound according to claim 1 , wherein R 1 is an amino group.
6 . The compound according to claim 1 , wherein R 1 is a nitro group.
7 . The compound according to claim 1 , wherein the compound is represented by the formula:
8 . The compound according to claim 1 , wherein the compound is represented by the formula:
9 . The compound according to claim 1 , wherein the compound is represented by the formula:
10 . The compound according to claim 1 , wherein the compound is represented by the formula:
11 . A pharmaceutical composition comprising a compound of claim 1 , in a pharmaceutically acceptable carrier.
12 . The pharmaceutical composition according to claim 11 , wherein the composition is formulated for intravenous administration.
13 . The pharmaceutical composition according to claim 11 , wherein the composition is formulated for oral administration.
14 . A compound according to Formula II:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
15 . A pharmaceutical composition comprising a compound of claim 14 , in a pharmaceutically acceptable carrier.
16 . The pharmaceutical composition according to claim 15 , wherein the composition is formulated for intravenous administration.
17 . The pharmaceutical composition according to claim 15 , wherein the composition is formulated for oral administration.
18 . A compound according to Formula III:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halo, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
19 . A pharmaceutical composition comprising a compound of claim 18 , in a pharmaceutically acceptable carrier.
20 . The pharmaceutical composition according to claim 19 , wherein the composition is formulated for intravenous administration.
21 . The pharmaceutical composition according to claim 19 , wherein the composition is formulated for oral administration.
22 . A compound according to Formula IV:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
23 . A pharmaceutical composition comprising a compound of claim 22 , in a pharmaceutically acceptable carrier.
24 . The pharmaceutical composition according to claim 23 , wherein the composition is formulated for intravenous administration.
25 . The pharmaceutical composition according to claim 23 , wherein the composition is formulated for oral administration.
26 . A compound according to Formula V:
wherein:
X 1 is independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 is CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
27 . A compound according to claim 26 , wherein:
X 1 is O; X 2 is C; and R 2 and R 3 are each H.
28 . A compound according to claim 26 , wherein A is
and R 7 and R 8 are each H.
29 . A compound according to claim 26 , wherein R 1 is alkoxy.
30 . A compound according to claim 26 , wherein the compound is represented by the formula:
31 . A pharmaceutical composition comprising a compound of claim 30 , in a pharmaceutically acceptable carrier.
32 . The pharmaceutical composition according to claim 31 , wherein the composition is formulated for intravenous administration.
33 . The pharmaceutical composition according to claim 31 , wherein the composition is formulated for oral administration.
34 . A compound according to Formula VI:
wherein:
X 1 is selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 is CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl.
35 . The compound according to claim 34 , wherein X 1 is O and X 2 is C.
36 . The compound according to claim 34 , wherein X 1 is NH and X 2 is C.
37 . The compound according to claim 34 , wherein X 1 is S and X 2 is C.
38 . The compound according to claim 34 , wherein X 1 is S and X 2 is N.
39 . The compound according to claim 34 , wherein the compound is represented by the formula
40 . The compound according to claim 34 , wherein the compound is represented by the formula
41 . The compound according to claim 34 , wherein the compound is represented by the formula
42 . The compound according to claim 34 , wherein the compound is represented by the formula
43 . The compound according to claim 34 , wherein the compound is represented by the formula
44 . The compound according to claim 34 , wherein the compound is represented by the formula
45 . The compound according to claim 34 , wherein the compound is represented by the formula
46 . The compound according to claim 34 , wherein the compound is represented by the formula
47 . The compound according to claim 34 , wherein the compound is represented by the formula
48 . The compound according to claim 34 , wherein the compound is represented by the formula
49 . The compound according to claim 34 , wherein the compound is represented by the formula
50 . A pharmaceutical composition comprising a compound of claim 34 , in a pharmaceutically acceptable carrier.
51 . The pharmaceutical composition according to claim 50 , wherein the composition is formulated for intravenous administration.
52 . The pharmaceutical composition according to claim 50 , wherein the composition is formulated for oral administration.
53 . A method of treating bovine viral diarrhea virus (BVDV) infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula I and Formula II:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the bovine viral diarrhea virus (BVDV) infection.
54 . The method according to claim 53 , wherein the compound is a compound of Formula I.
55 . The method according to claim 53 , wherein the compound is represented by the formula:
56 . The method according to claim 53 , wherein the subject is a cow.
57 . The method according to claim 53 , wherein the subject is an embryo.
58 . The method according to claim 53 , wherein the compound is administered intravenously.
59 . The method according to claim 53 , wherein the compound is administered orally.
60 . A method of treating bovine viral diarrhea virus (BVDV) infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula III and Formula IV:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the bovine viral diarrhea virus (BVDV) infection.
61 . A method of treating bovine viral diarrhea virus (BVDV) infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula V and Formula VI:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the bovine viral diarrhea virus (BVDV) infection.
62 . The method according to claim 61 , wherein the subject is a cow.
63 . The method according to claim 61 , wherein the subject is an embryo.
64 . The method according to claim 61 , wherein the compound is administered intravenously.
65 . The method according to claim 61 , wherein the compound is administered orally.
66 . The method according to claim 61 , wherein the compound is represented by the formula:
67 . The method according to claim 61 , wherein the compound is represented by the formula
68 . The method according to claim 61 , wherein the compound is represented by the formula
69 . The method according to claim 61 , wherein the compound is represented by the formula
70 . The method according to claim 61 , wherein the compound is represented by the formula
71 . The method according to claim 61 , wherein the compound is represented by the formula
72 . The method according to claim 61 , wherein the compound is represented by the formula
73 . The method according to claim 61 , wherein the compound is represented by the formula
74 . The method according to claim 61 , wherein the compound is represented by the formula
75 . The method according to claim 61 , wherein the compound is represented by the formula
76 . The method according to claim 61 , wherein the compound is represented by the formula
77 . The method according to claim 61 , wherein the compound is represented by the formula
78 . A method of treating hepatitis C infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula I and Formula II:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the hepatitis C infection.
79 . The method according to claim 78 , wherein the compound is a compound of Formula I.
80 . The method according to claim 78 , wherein the compound is represented by the formula:
81 . The method according to claim 78 , wherein the subject is a human.
82 . The method according to claim 78 , wherein the compound is administered intravenously.
83 . The method according to claim 78 , wherein the compound is administered orally.
84 . A method of treating hepatitis C infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula III and Formula IV:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the hepatitis C infection.
85 . A method of treating hepatitis C infection in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula V and Formula VI:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the hepatitis C infection.
86 . The method according to claim 85 , wherein the subject is a human.
87 . The method according to claim 85 , wherein the compound is administered intravenously.
88 . The method according to claim 85 , wherein the compound is administered orally.
89 . The method according to claim 85 , wherein the compound is represented by the formula:
90 . The method according to claim 85 , wherein the compound is represented by the formula
91 . The method according to claim 85 , wherein the compound is represented by the formula
92 . The method according to claim 85 , wherein the compound is represented by the formula
93 . The method according to claim 85 , wherein the compound is represented by the formula
94 . The method according to claim 85 , wherein the compound is represented by the formula
95 . The method according to claim 85 , wherein the compound is represented by the formula
96 . The method according to claim 85 , wherein the compound is represented by the formula
97 . The method according to claim 85 , wherein the compound is represented by the formula
98 . The method according to claim 85 , wherein the compound is represented by the formula
99 . The method according to claim 85 , wherein the compound is represented by the formula
100 . The method according to claim 85 , wherein the compound is represented by the formula
101 . A method of treating a member of the Flaviviridae family of viruses in a subject in need of such treatment, comprising administering to the subject a compound selected from the group consisting of Formula I and Formula II:
wherein:
X 1 and X 3 are each independently selected from the group consisting of O, S and NR 9 , wherein R 9 is H or alkyl;
X 2 and X 4 are each independently CH or N;
A is selected from the group consisting of H, alkyl, aryl,
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, alkylhalide, amidine, nitro and amino groups;
R 6 is H, alkyl or aryl; and
R 7 and R 8 are each independently selected from the group consisting of H and alkyl;
or a pharmaceutically acceptable salt thereof, in an amount sufficient to treat the bovine viral diarrhea virus (BVDV) infection.
102 . The method according to claim 101 , wherein the compound is a compound of Formula II.
103 . The method according to claim 101 , wherein the compound is represented by the formula:
104 . The method according to claim 101 , wherein the compound is represented by the formula:
105 . The method according to claim 101 , wherein the compound is administered intravenously.
106 . The method according to claim 101 , wherein the compound is administered orally.Cited by (0)
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