CYCLIC PHOSPHORAMIDATE COMPOUNDS
Provided herein are cyclic phosphoramidate compounds, their preparation and their uses, such as treating liver or non-liver diseases or conditions.
1 . A compound of Formula I or II:
wherein:
R 1 is independently selected from the group consisting of an optionally substituted C 1 -C 8 alkyl and an optionally substituted benzyl;
R 2a and R 2b are each independently selected from the group consisting of H, OR 7 , halo, CN, and optionally substituted C 1 -C 10 alkyl;
R 3 and R 4 are independently selected from the group consisting of H, OH, halo, CN, N 3 , and an optionally substituted C 1 -C 10 alkyl;
R 5a and R 5b are independently H or an optionally substituted C 1 -C 10 alkyl; or R 5a and R 5b , taken together with the atom to which they are attached form a three to seven membered ring;
Y is H or —OR 6 ;
R 6 is an optionally substituted C 1 -C 8 alkyl or optionally substituted benzyl; or
R 6 and R 1 are taken together with the atom to which they are attached form a five to ten membered ring;
R 7 is independently selected from a group of H, C(O)R 8 , C(O) OR 8 , and C(O)NHR 8 ;
each R 8 is independently selected from a group of H and an optionally substituted C 1 -C 10 alkyl; and
BASE 1 is selected from the group consisting of
BASE 2 is selected from the group consisting of
R 9 is H, halo, or optionally substituted alkyl;
R 10 is selected from the group consisting of H, optionally substituted C 1 -C 10 alkyl, an optionally substituted C 1 -C 10 acyl, optionally substituted C 1 -C 10 alkyl-OC(O)—, optionally substituted (C 6-10 aryl)-C(O)—, and optionally substituted (C 6-10 aryl)-OC(O)—;
R 11 is selected from the group consisting of OH, NH 2 , NHOR 7 , an optionally substituted C 1 -C 10 alkyloxy, an optionally substituted C 1 -C 10 alkylamino, an optionally substituted C 1 -C 10 acyloxy, an optionally substituted C 1 -C 10 acylamino, and an optionally substituted C 1 -C 10 alkyl-OC(O)NH—; and
R 12 is selected from the group consisting of H, NH 2 , optionally substituted C 1 -C 10 alkylamino, optionally substituted C 1 -C 10 acylamino, and optionally substituted C 1 -C 10 alkyl-OC(O) NH—;
with the proviso that when BASE 2 is
R 11 is alkoxy, and R 12 is NH 2 , then R 2b is not F.
2 . The compound of claim 1 , wherein R 1 is selected from the group consisting of: methyl, ethyl, propyl, butyl, pentyl, and benzyl.
3 . The compound of claim 1 , wherein R 2a is H, methyl, OR 7 , Cl, or F.
4 . The compound of claim 1 , wherein R 2b is H, methyl, OR 7 , Cl, or F.
5 . The compound of claim 1 , wherein R 2a is H and R 2b is H; or wherein R 2a is methyl and R 2b is fluoro; or wherein R 2a and R 2b are each halo; or wherein R 2a is H and R 2b is OR 7 ; or wherein R 2a is OR 7 and R 2b is H.
6 . (canceled)
7 . (canceled)
8 . (canceled)
9 . (canceled)
10 . (canceled)
11 . The compound of claim 1 , wherein R 3 is H, methyl, or halo.
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . The compound of claim 1 , wherein R 4 is H, methyl, or halo.
16 . (canceled)
17 . (canceled)
18 . (canceled)
19 . The compound of claim 1 , wherein R 5a is H or an optionally substituted C 1 -C 10 alkyl.
20 . The compound of claim 1 , wherein R 5b is H or an optionally substituted C 1 -C 10 alkyl.
21 . The compound of claim 1 , wherein R 5a is H and R 5b is methyl, or wherein R 5a is methyl and R 5b is H.
22 . (canceled)
23 . The compound of claim 1 , wherein R 5a and R 5b , taken together with the atom to which they are attached, form a three to seven membered ring.
24 . The compound of claim 1 , wherein Y is H.
25 . The compound of claim 1 , wherein Y is —OR 6 , and R 6 is an optionally substituted C 1 -C 8 alkyl.
26 . The compound of claim 1 , wherein Y is —OR 6 ; and R 6 and R 1 are taken together with the atom to which they are attached form a five to ten membered ring.
27 . The compound of claim 1 , wherein R 7 is H.
28 . The compound of claim 1 , wherein R 7 is C(O)R 8 , C(O) OR 8 , or C(O)NHR 8 ; and R 8 is H or optionally substituted C 1 -C 10 alkyl.
29 . The compound of claim 1 , wherein, BASE 1 is
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . (canceled)
36 . (canceled)
37 . (canceled)
38 . (canceled)
39 . (canceled)
40 . (canceled)
41 . The compound of claim 1 , wherein R 9 is H, halo, or unsubstituted C 1 -C 10 alkyl.
42 . (canceled)
43 . (canceled)
44 . The compound of claim 1 , wherein R 11 is selected from the group consisting of NH 2 , an optionally substituted C 1 -C 10 acylamino, and an optionally substituted C 1 -C 10 alkylamino.
45 . (canceled)
46 . The compound of claim 1 , wherein R 12 is H, NH 2 , or an optionally substituted C 1 -C 10 acylamino.
47 . (canceled)
48 . (canceled)
49 . A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
50 . A pharmaceutical composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable excipient.
51 . (canceled)
52 . A method of treating a disease, disorder or condition comprising administering an effective amount of one or more compound of claim 1 .
53 . The method of claim 52 , wherein the disease, disorder or condition is a disease, disorder or condition of the liver.
54 . (canceled)
55 . (canceled)
56 . (canceled)
57 . (canceled)
58 . (canceled)
59 . (canceled)
60 . (canceled)
61 . (canceled)