US2017137429A1PendingUtilityA1
Anti-influenza compositions and methods
Est. expiryMay 14, 2033(~6.8 yrs left)· nominal 20-yr term from priority
A61K 45/06A61K 31/519C07D 519/00C07D 471/04A61P 31/16A61P 31/12C07D 487/04A61P 43/00A61K 31/13Y02A50/30
53
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Claims
Abstract
Disclosed are novel compounds comprising an imino-ribose derivative covalently linked to a carbocycle or heterocycle. Pharmaceutical compositions comprising the compounds of the invention are also described. Methods of inhibition, treatment and/or suppression of viral infections with the compounds of the invention are also described. The compositions or methods may optionally comprise one or more additional anti-viral agents.
Claims
exact text as granted — not AI-modified1 . A compound of formula I:
wherein
R 1 is selected from the group consisting of
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), C(═NR 10 ), OC(═O), OC(═S), OC(═NR 10 ), N(R 11 )C(═O), N(R 11 )C(═S), or N(R 11 )C(═NR 10 );
R 4 is OH or N(R 15 ) 2 ;
R 5 is H or N(R 15 ) 2 ;
R 6 is R 11 , C(═O)—R 11 , or SO 2 —R 11 ;
R 7 is H or R 12 , wherein R 12 is optionally substituted with one or more groups selected from lower alkyl, OR 11 , O—C(═)—R 11 , O—C(═O)O—R 11 , and O—C(═O)N(R 11 ) 2 ;
R 8 is OR 11 , O—C(═)—R 11 , O—C(═O)O—R 11 , O—C(═O)N(R 11 ) 2 , O—C(═S)—R 11 , O—C(═S)O—R 11 , O—C(═S)N(R 11 ) 2 , N(R 11 ) 2 , N(R 11 )C(═O)—R 11 , N(R 11 )C(═O)O(R 11 ) 2 , N(R 11 )C(═S)—R 11 , N(R 11 )C(═S)O—R 11 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ;
R 9 is H, OH, O—C(═O)O—R 11 , O—C(═O)N(R 11 ) 2 , O—C(═S)—R 11 , O—C(═S)O—R 11 , O—C(═S)N(R 11 ) 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —R 13 —R 14 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl, lower alkenyl, lower alkynyl, aryl or heteroaryl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently halogen, R 10 , OC(═)R 11 , OC(═S)R 11 , OC(═NR 10 )R 11 , OC(═O)R 11 , OC(═S)OR 11 , OC(═NR 10 )OR 11 , OC(═O)N(R 11 ) 2 , OC(═S)N(R 11 ) 2 , OC(═NR 10 )N(R 11 ) 2 , N(R 11 )C(═O)R 11 , N(R 11 )C(═S)R 11 , N(R 11 )C(═NR 10 )R 11 , N(R 11 )C(═O)OR 11 , N(R 11 )C(═S)OR 11 , N(R 11 )C(═NR 10 )OR 11 , N(R 11 )C(═)N(R 11 ) 2 , N(R 11 )C(═S)N(R 11 ) 2 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ;
or a pharmaceutically acceptable salt thereof.
2 . (canceled)
3 . The compound of claim 1 , wherein R 1 is selected from the group consisting of
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—R 11 , or SO 2 —R 11 ;
R 7 is lower alkyl, optionally substituted with one or more groups selected from lower alkyl, OR 11 , O—C(═O)—R 11 , O—C(═O)O—R 11 , and O—C(═O)N(R 11 ) 2 ;
R 8 is OR 11 , O—C(═O)—R 11 , O—C(═O)O—R 11 , O—C(═O)N(R 11 ) 2 , O—C(═S)—R 11 , O—C(═S)N(R 11 ) 2 , N(R 11 ) 2 , N(R 11 )C(═O)O(R 11 ) 2 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ;
R 9 is H, OH, O—C(═O)O—R 11 , or O—C(═O)N(R 11 ) 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
4 . (canceled)
5 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)-lower alkyl;
R 7 is lower alkyl substituted with one or more lower alkyl;
R 8 is N(H)C(═NH)NH 2 ;
R 9 is H or OH;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
6 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is —CH(CH 2 CH 3 ) 2 ;
R 8 is N(H)C(═NH)NH 2 ;
R 9 is OH;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
7 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O or S;
R 3 is a bond or C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is —CH(CH 2 CH 3 ) 2 ;
R 8 is N(H)C(═NH)NH 2 ;
R 9 is OH;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , or R 12 —OC(═O)—R 13 ; wherein each R 12 and R 13 are optionally substituted with R 15 ;
R 11 is independently H, or lower alkyl;
R 12 is independently lower alkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, aryl, or heteroaryl; and
R 15 is independently lower alkyl, N(R 11 ) 2 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
8 . (canceled)
9 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)-lower alkyl;
R 7 is lower alkyl substituted with one or more lower alkyl;
R 8 is NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
10 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is —CH(CH 2 CH 3 ) 2 ;
R 8 is NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
11 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O or S;
R 3 is a bond or C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is —CH(CH 2 CH 3 ) 2 ;
R 8 is NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , or R 12 —OC(═O)—R 13 ; wherein each R 12 and R 13 are optionally substituted with R 15 ;
R 11 is independently H, or lower alkyl;
R 12 is independently lower alkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, aryl, or heteroaryl; and
R 15 is independently lower alkyl, N(R 11 ) 2 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
12 . (canceled)
13 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)-lower alkyl;
R 7 is lower alkyl substituted with one or more OR 11 ;
R 8 is NH 2 C(═NH)NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
14 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), or N(R 11 )C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is 1,2,3-trihydroxypropyl;
R 8 is NH 2 C(═NH)NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently R 10 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
15 . The compound of claim 1 , wherein R 1 is
R 2 is a bond, O or S;
R 3 is a bond or C(═O);
R 4 is OH or NH 2 ;
R 5 is H or NH 2 ;
R 6 is C(═O)—CH 3 ;
R 7 is 1,2,3-trihydroxypropyl;
R 8 is NH 2 C(═NH)NH 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —O—R 13 , or R 12 —OC(═O)—R 13 ; wherein each R 12 and R 13 are optionally substituted with R 15 ;
R 11 is independently H, or lower alkyl;
R 12 is independently lower alkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, aryl, or heteroaryl; and
R 15 is independently lower alkyl, N(R 11 ) 2 , N(R 11 )C(═O)R 11 , or N(R 11 )C(═O)OR 11 ;
or a pharmaceutically acceptable salt thereof.
16 . (canceled)
17 . The compound of claim 1 , wherein the compound is selected from the group consisting of:
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof;
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof; and
or a pharmaceutically acceptable salt thereof.
18 . (canceled)
19 . (canceled)
20 . A pharmaceutical composition, comprising a compound of claim 1 ; and a pharmaceutically acceptable carrier.
21 . A method for inhibiting, treating or suppressing a viral infection, comprising administering to a subject in need thereof an effective amount of a compound of formula I:
wherein
R 1 is selected from the group consisting of
R 2 is a bond, O, or S;
R 3 is a bond, C(═O), C(═S), C(═NR 10 ), OC(═O), OC(═S), OC(═NR 10 ), N(R 11 )C(═O), N(R 11 )C(═S), or N(R 11 )C(═NR 10 );
R 4 is OH or N(R 15 ) 2 ;
R 5 is H or N(R 15 ) 2 ;
R 6 is R 11 , C(═O)—R 11 , or SO 2 —R 11 ;
R 7 is H or R 12 , wherein R 12 is optionally substituted with one or more groups selected from lower alkyl, OR 11 , O—C(═)—R 11 , O—C(═O)O—R 11 , and O—C(═O)N(R 11 ) 2 ;
R 8 is OR 11 , O—C(═)—R 11 , O—C(═O)O—R 11 , O—C(═O)N(R 11 ) 2 , O—C(═S)—R 11 , O—C(═S)O—R 11 , O—C(═S)N(R 11 ) 2 , N(R 11 ) 2 , N(R 11 )C(═O)—R 11 , N(R 11 )C(═O)O(R 11 ) 2 , N(R 11 )C(═S)—R 11 , N(R 11 )C(═S)O—R 11 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ;
R 9 is H, OH, O—C(═O)O—R 11 , O—C(═O)N(R 11 ) 2 , O—C(═S)—R 11 , O—C(═S)O—R 11 , O—C(═S)N(R 11 ) 2 ;
B is a bond, R 12 , R 12 —R 13 , R 12 —R 13 —R 14 , R 12 —O—R 13 , R 12 —OC(═O)—R 13 , R 12 —N(R 11 )C(═O)—R 13 , R 12 —OC(═O)—OR 13 , R 12 —OC(═O)—N(R 11 )R 13 , R 12 —N(R 11 )C(═O)—OR 13 , or R 12 —N(R 11 )C(═O)—N(R 11 )R 13 ; wherein each R 12 , R 13 , and R 14 are optionally substituted with one or more R 15 ;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, or lower alkyl optionally substituted with one or more lower alkyl, lower alkenyl, lower alkynyl, aryl or heteroaryl;
R 12 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 13 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl;
R 14 is independently lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently halogen, R 10 , OC(═O)R 11 , OC(═S)R 11 , OC(═NR 10 )R 11 , OC(═O)OR 11 , OC(═S)OR 11 , OC(═NR 10 )OR 11 , OC(═O)N(R 11 ) 2 , OC(═S)N(R 11 ) 2 , OC(═NR 10 )N(R 11 ) 2 , N(R 11 )C(═O)R 11 , N(R 11 )C(═S)R 11 , N(R 11 )C(═NR 10 )R 11 , N(R 11 )C(═O)OR 11 , N(R 11 )C(═S)OR 11 , N(R 11 )C(═NR 10 )R 11 , N(R 11 )C(═)N(R 11 ) 2 , N(R 11 )C(═S)N(R 11 ) 2 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ;
or a pharmaceutically acceptable salt thereof.
22 . (canceled)
23 . The method of claim 21 , wherein a neuraminidase inhibitor is generated following administration of the compound of formula I, wherein the neuraminidase inhibitor is selected from the group consisting of oseltamivir, zanamivir and peramivir, or a pharmaceutically acceptable salt thereof.
24 . The method of claim 21 , wherein a neuraminidase inhibitor is generated following administration of the compound of formula I, wherein the neuraminidase inhibitor is peramivir, or a pharmaceutically acceptable salt thereof.
25 . (canceled)
26 . (canceled)
27 . The method of claim 21 , wherein a polymerase inhibitor is generated following administration of the compound of formula I, wherein the polymerase inhibitor is comprised of compound (A)
wherein
R 4 is NH 2 ; and
R 5 is hydrogen;
or a pharmaceutically acceptable salt thereof.
28 . (canceled)
29 . The method of claim 21 , wherein a neuraminidase inhibitor and a polymerase inhibitor are generated following administration of the compound of formula I, wherein the neuraminidase inhibitor is selected from the group consisting of oseltamivir, zanamivir and peramivir, or a pharmaceutically acceptable salt thereof; and
the polymerase inhibitor is comprised of compound (A)
wherein
R 4 is N(R 15 ) 2 ;
R 5 is hydrogen;
R 10 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl, OR 11 , or N(R 11 ) 2 ;
R 11 is independently H, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, or heteroaryl; and
R 15 is independently halogen, R 10 , OC(═O)R 11 , OC(═S)R 11 , OC(═NR 10 )R 11 , OC(═O)OR 11 , OC(═S)OR 11 , OC(═NR 10 )OR 11 , OC(═O)N(R 11 ) 2 , OC(═S)N(R 11 ) 2 , OC(═NR 10 )N(R 11 ) 2 , N(R 11 )C(═O)R 11 , N(R 11 )C(═S)R 11 , N(R 11 )C(═NR 10 )R 11 , N(R 11 )C(═O)OR 11 , N(R 11 )C(═S)OR 11 , N(R 11 )C(═NR 10 )OR 11 , N(R 11 )C(═O)N(R 11 ) 2 , N(R 11 )C(═S)N(R 11 ) 2 , or N(R 11 )C(═NR 10 )N(R 11 ) 2 ; or
a pharmaceutically acceptable salt thereof.
30 . The method of claim 21 , wherein a neuraminidase inhibitor is generated following administration of the compound of formula I, wherein the neuraminidase inhibitor is peramivir, or a pharmaceutically acceptable salt thereof; and the polymerase inhibitor is comprised of compound (A)
wherein
R 4 is NH 2 ; and
R 5 is hydrogen; or
a pharmaceutically acceptable salt thereof.
31 - 37 . (canceled)
38 . The method of claim 21 , wherein the compound of formula I is selected from the group consisting of:
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof;
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof; and
or a pharmaceutically acceptable salt thereof.
39 . (canceled)
40 . (canceled)
41 . The method of claim 21 , wherein the viral infection is influenza.
42 . The method of claim 21 , further comprising administering to the subject an effective amount of an additional anti-viral agent.
43 . The method of claim 42 , wherein the additional anti-viral agent is rimantadine or amantadine.
44 . The method of claim 21 , wherein the compound of formula I is administered orally, intravenously, or intramuscularly.
45 . (canceled)
46 . (canceled)
47 . The method of claim 21 , wherein the subject is a mammal.
48 . The method of claim 21 , wherein the subject is a human.
49 . The method of claim 21 , wherein the subject is an avian.
50 . The method of claim 38 , wherein the viral infection is influenza.
51 . The method of claim 38 , further comprising administering to the subject an effective amount of an additional anti-viral agent.
52 . The method of claim 51 , wherein the additional anti-viral agent is rimantadine or amantadine.
53 . The method of claim 38 , wherein the compound of formula I is administered orally, intravenously, or intramuscularly.
54 . The method of claim 38 , wherein the subject is a mammal.
55 . The method of claim 38 , wherein the subject is a human.
56 . The method of claim 38 , wherein the subject is an avian.
57 . The pharmaceutical composition of claim 20 , wherein the compound is selected selected from the group consisting of:
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof;
wherein n is an integer from 1 to 6; or a pharmaceutically acceptable salt thereof; and
or a pharmaceutically acceptable salt thereof.Join the waitlist — get patent alerts
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