Anti-viral 7-deaza D-nucleosides and uses thereof
The present invention relates generally to anti-viral compounds, particularly anti-viral 7-deaza D-nucleosides and analogues, or derivatives thereof. The invention also relates to the use of such compounds to treat or prevent hepatitis B virus (HBV) infections, and to the use of such compounds to examine the biological mechanisms of HBV infection.
1 . An anti-viral compound and pharmaceutically acceptable salts thereof, according to structural formula (I):
wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, Cl, OH, C 1 -C 4 alkoxy, NH 2 , or NHZR 5 ;
each of R 2 and R 3 are independently hydrogen, C 1 -C 6 alkyl, methyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, Cl, I, Br, F, heterocyclyl, or R 2 and R 3 together with the carbons to which they are attached form a 5-membered ring;
R 4 is hydrogen, OH, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 4 alkoxy, NH 2 , NHZR 5 or N(R 5 ) 2 ;
each R 5 is independently C 1 -C 6 alkyl, C 5 -C 6 cycloalkyl, or aryl;
each of R 6 , R 7 , R 8 and R 9 are independently hydrogen, OH, C 1 -C 6 alkyl, NH 2 , NHZR 5 , F, Cl, or Br, or R 6 , R 7 , R 8 and R 9 form an epoxide or a double bond;
each of Y and Y′ are independently N or CH; and
Z is CO, C(O)NH or SO 2 .
2 . The compound according to claim 1 wherein R 1 is NH 2 ; R 2 is a halogen or C 1 -C 4 alkyl; and R 3 and R 4 are hydrogen.
3 . The compound according to claim 1 wherein R 1 is NH 2 ; R 2 is hydrogen or a halogen; R 3 is a halogen or C 1 -C 4 alkyl; and R 4 is hydrogen.
4 . The compound according to claim 1 wherein R 1 is NH 2 ; each of R 2 and R 3 are independently hydrogen or a halogen; and R 4 is C 1 -C 4 alkyl.
5 . The compound according to claim 1 wherein R 1 is NH 2 ; R 2 and R 3 together with the carbon atoms they are attached to form a pentene ring; and R 4 is hydrogen.
6 . The compound according to claim 1 wherein R 1 is hydrogen or C 1 -C 4 alkyl; each of R 2 and R 3 are independently hydrogen or a halogen; and R 4 is hydrogen.
7 . The compound according to claim 1 wherein R 1 is NH2; each of R 2 and R 3 are independently hydrogen or a halogen; and R 4 is NHZR 5 ; wherein Z and R 5 are as defined in claim 1 .
8 . The compound according to claim 1 wherein R 6 , R 7 , R 8 and R 9 are hydrogen.
9 . The compound according to claim 1 wherein R 6 , R 8 and R 9 are hydrogen; and R 7 is OH.
10 . The compound according to claim 1 wherein R 6 and R 9 are hydrogen; R 7 is C 1 -C 4 alkyl; and R 8 is OH.
11 . The compound according to claim 1 wherein R 6 and R 9 are hydrogen; R 7 is NHZR 5 ; and R 8 is OH; wherein Z and R 5 are as defined in claim 1 .
12 . The compound according to claim 1 wherein R 6 and R 9 are hydrogen; R 7 is F; and R 8 is OH.
13 . The compound according to claim 1 wherein R 6 is C 1 -C 4 alkyl, R 7 and R 9 are hydrogen; and R 8 is OH.
14 . The compound according to claim 1 wherein said compound has structure (II):
15 . A pharmaceutical composition comprising a compound according to any one of claims 1 to 14 and a pharmaceutically acceptable carrier, excipient or diluent.
16 . A method of treating or preventing a viral infection, comprising administering to a subject in need thereof an anti-viral compound according to any one of claims 1 to 14 in an amount effective to treat or prevent a viral infection.
17 . The method of claim 16 in which said anti-viral compound is administered orally.
18 . The method of claim 16 wherein said anti-viral compound is administered systemically.
19 . The method of claim 16 wherein said viral infection is caused by hepatitis B virus (HBV).
20 . A method of treating or preventing a viral infection, comprising administering to a subject in need thereof a composition according to claim 15 in an amount effective to treat or prevent a viral infection.