COMPOUNDS AND METHODS FOR TREATMENT OF VIRAL INFECTIONS
Compounds and methods of using said compounds, singly or in combination with additional agents, and salts or pharmaceutical compositions of said compounds for the treatment of viral infections are disclosed.
1 . A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 are taken together to form —OC(═O)O—, —OP(═O)(OH)O—, or —OCHR 6 O—;
R 3 is —C(═O)OR 7 ;
R 7 is C 1 -C 20 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 10 carbocyclyl, C 6 -C 10 aryl, 4 to 8 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S, or 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S;
wherein C 1 -C 20 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 10 carbocyclyl, C 6 -C 10 aryl, 4 to 8 membered heterocyclyl, or 5 to 6 membered heteroaryl of R 7 is optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 8 alkyl, halogen, cyano, carbonyl, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , —OP(═O)(OR 8 ) 2 , C 3 -C 8 carbocyclyl, 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S, 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S, and phenyl;
wherein substituent C 3 -C 8 carbocyclyl of R 7 is optionally substituted with one, two, or three substituents independently selected from C 1 -C 8 alkyl, halogen, —CF 3 , cyano, —CH 2 CN, and phenyl,
wherein substituent 4 to 6 membered heterocyclyl of R 7 is optionally substituted with one, two, or three substituents independently selected from carbonyl and C 1 -C 6 alkyl, and
wherein substituent phenyl of R 7 is optionally substituted with one, two or three substituents independently selected from halo, cyano, C 1 -C 6 alkyl, and —OR 8 ;
R 6 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S, or C 6 -C 10 aryl;
wherein 5 to 6 membered heteroaryl and C 6 -C 10 aryl of R 6 are each, independently, optionally substituted with one, two, or three substituents independently selected from halo, cyano, C 1 -C 6 alkoxy, and C 1 -C 6 alkyl;
each R 8 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, and 4 to 6 membered heterocyclyl;
wherein C 1 -C 6 alkyl of R 8 is optionally substituted with C 3 -C 6 cycloalkyl or 4 to 6 membered heterocyclyl;
each R 9 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 3 -C 6 cycloalkyl;
each R 10 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 3 -C 6 cycloalkyl;
Base is
R 11 is C 1 -C 6 alkyl optionally substituted with —OP(═O)(OH)(OR 14 );
R 12 is H, C 1 -C 6 alkyl, —C(═O)R 13 , or —C(═O)OR 13 ;
each R 13 is independently H or C 1 -C 8 alkyl; wherein C 1 -C 8 alkyl of R 13 is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, —OP(═O)(OH)(OR 14 ), and phenyl, wherein substituent phenyl of R 13 is optionally substituted with —OP(═O)(OH)(OR 14 ); and
each R 14 is independently H, C 1 -C 8 alkyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, or 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S; wherein C 1 -C 8 alkyl of R 14 is optionally substituted with one, two or three substituents independently selected from the group consisting of halogen, cyano, and phenyl.
2 .- 14 . (canceled)
15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are taken together to form —OC(═O)O—.
16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are taken together to form —OP(═O)(OH)O—.
17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are taken together to form —OCHR 6 O—.
18 .- 40 . (canceled)
41 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H.
42 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 6 is C 1 -C 6 alkyl.
43 . (canceled)
44 . The compound of claim 17 , or pharmaceutically acceptable salt thereof, wherein R 6 is C 1 -C 6 alkoxy.
45 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 6 is C 6 -C 10 aryl.
46 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 6 is phenyl.
47 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 20 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S or 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S; wherein C 1 -C 20 alkyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, 4 to 6 membered heterocyclyl, or 5 to 6 membered heteroaryl of R 7 are each optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 8 alkyl, halogen, cyano, carbonyl, —N 3 , —OR 8 —NR 9 R 10 , —OP(═O)(OH) 2 , —OP(═O)(OR 8 ) 2 , C 3 -C 8 carbocyclyl, 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S, 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S, and phenyl; wherein substituent C 3 -C 8 carbocyclyl of R 7 is optionally substituted with one, two, or three substituents independently selected from C 1 -C 8 alkyl, halogen, —CF 3 , cyano, —CH 2 CN, and phenyl, wherein substituent 4 to 6 membered heterocyclyl of R 7 is optionally substituted with one, two, or three substituents independently selected from carbonyl and C 1 -C 6 alkyl, and wherein substituent phenyl of R 7 is optionally substituted with one, two or three substituents independently selected from halo, cyano, C 1 -C 6 alkyl, and OR 8 .
48 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S or 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S; wherein C 1 -C 8 alkyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, 4 to 6 membered heterocyclyl, and 5 to 6 membered heteroaryl of R 7 are each optionally substituted with one, two, or three substituents independently selected from the group consisting of —OR 8 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two, or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
49 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl, C 3 -C 8 carbocyclyl, C 6 -C 10 aryl, 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S or 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S; wherein C 1 -C 8 alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of —OR 8 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl.
50 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, or C 2 -C 8 alkynyl; wherein C 1 -C 8 alkyl, C 2 -C 8 alkenyl, or C 2 -C 8 alkynyl are each, independently, optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl;
51 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
52 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 6 alkyl optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
53 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl optionally substituted with one substituents selected from the group consisting of —OR 8 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl.
54 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 6 alkyl optionally substituted with one substituents selected from the group consisting of —OR 8 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl.
55 .- 69 . (canceled)
70 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 8 alkyl.
71 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1 -C 6 alkyl.
72 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is
73 .- 76 . (canceled)
77 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 3 -C 8 carbocyclyl optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
78 .- 82 . (canceled)
83 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is C 6 -C 10 aryl optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 8 alkyl, halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein substituent phenyl of R 7 is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
84 .- 89 . (canceled)
90 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is 4 to 6 membered heterocyclyl containing 1, 2, or 3 heteroatoms selected from N, O, and S optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
91 .- 100 . (canceled)
101 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is 5 to 6 membered heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, and S optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, cyano, —N 3 , —OR 8 , —NR 9 R 10 , —OP(═O)(OH) 2 , C 3 -C 8 carbocyclyl and phenyl; wherein phenyl is optionally substituted with one, two or three substituents independently selected from halo, cyano, and C 1 -C 6 alkyl.
102 .- 106 . (canceled)
107 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is
108 .- 125 . (canceled)
126 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Base is
127 . The compound of claim 126 , or a pharmaceutically acceptable salt thereof, wherein R 12 is H.
128 . The compound of claim 126 , or a pharmaceutically acceptable salt thereof, wherein R 12 is C 1 -C 6 alkyl.
129 .- 171 . (canceled)
172 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
173 . (canceled)
174 . (canceled)
175 . A method of treating or preventing a viral infection in a human in need thereof, wherein the method comprises administering to the human the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
176 .- 212 . (canceled)
213 . The compound of claim 1 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.
214 . The compound of claim 1 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.
215 . The compound of claim 1 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.