Imidazo[1,2-α]pyrazine derivatives
View Patent ↗The present invention provides, among other things, imidazo[1,2-α]pyrazine derivatives according for Formula (Ia) or Formula (Ib). The derivatives are useful in any method which other coelenterazines have been used. For example, the derivatives may be used in a bioluminogenic method to detect the presence of certain compounds or molecules.
1. A compound of formula (Ia) or formula (Ib):
wherein R 2 is selected from the group consisting of
or C 2-5 straight chain alkyl;
R 6 is selected from the group consisting of —H, —OH, —NH 2 , —OC(O)R or —OCH 2 OC(O)R;
R 8 is selected from the group consisting of —CH 2 C 6 H 5 , H or lower cycloalkyl;
W is —NH 2 , halo, —OH, —NHC(O)R, —CO 2 R;
X is —S—, —O— or —NR 22 —;
Y is —H, —OH, or —OR 11 ;
Z is —CH— or —N—;
each R 11 is independently —C(O)R″ or —CH 2 OC(O)R″;
R 22 is H;
each R is independently C 1-7 straight-chain alkyl or C 3-7 branched alkyl;
R″ is C 1-7 straight-chain alkyl or C 3-7 branched alkyl;
with the proviso that when R 2 is
or
R 8 is not —CH 2 C 6 H 5 ;
with the proviso that when R 2 is —CH 2 C 6 H 5 , R 8 is lower cycloalkyl; and
with the proviso that when R 6 is NH 2 , R 2 is,
or C 2-5 straight chain alkyl;
or R 8 is not —CH 2 C 6 H 5 .
2. A compound according to claim 1 ,
wherein R 2 is
and
X is —O— or —S—.
3. A compound according to claim 1 , wherein R 2 is C 2-5 straight-chain alkyl.
4. A compound according to claim 1 , wherein R 8 is lower cycloalkyl or H.
5. A compound according to claim 1 , wherein R 8 is —CH 2 C 6 H 5 .
6. A compound according to claim 1 , wherein R 11 is —CH 2 OC(O)C(CH 3 ) 3 .
7. A compound according to claim 1 , wherein R″ is —C(CH 3 ) 3 , —CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , or —CH 2 CH(CH 3 ) 2 .
8. A kit comprising a compound according to claim 1 .
9. A method for detecting luminescence in a sample comprising contacting said sample with a compound according to claim 1 .
10. The method of claim 7 , wherein the sample contains live cells.
11. The method of claim 7 , wherein the sample contains a coelenterazine-utilizing luciferase.
12. A method for detecting luminescence in a transgenic animal comprising administering to said transgenic animal a compound according to claim 1 .
13. A compound of formula (Ia) or formula (Ib):
wherein R 2 is selected from the group consisting of
R 6 is selected from the group consisting of —H, —OH, —NH 2 , —OC(O)R or —OCH 2 OC(O)R;
R 8 is selected from the group consisting of —CH 2 C 6 H 5 , —C(R 3 )(R 4 )H, H or lower cycloalkyl;
wherein R 3 and R 4 are both H or both C 1-2 alkyl;
X is —NR 22 —;
Z is —CH— or —N—;
R 22 is CH 3 or CH 2 CH 3 ;
each R is independently C 1-7 straight-chain alkyl or C 3-7 branched alkyl;
each R 11 is independently —C(O)R″ or —CH 2 OC(O)R″; and
R″ is C 1-7 straight-chain alkyl or C 3-7 branched alkyl.
14. A compound according to claim 13 , wherein R 8 is —C(R 3 )(R 4 )H, lower cycloalkyl or H.
15. A compound according to claim 13 , wherein R 8 is —CH 2 C 6 H 5 .
16. A compound according to claim 13 , wherein R 11 is —CH 2 OC(O)C(CH 3 ) 3 .
17. A compound of formula (Ia) or formula (Ib):
wherein R 2 is selected from the group consisting of
or C 2-5 straight chain alkyl;
R 6 is selected from the group consisting of —H, —OH, —NH 2 , —OC(O)R or —OCH 2 OC(O)R;
R 8 is selected from the group consisting of —CH 2 C 6 H 5 , —C(R 3 )(R 4 )H, H or lower cycloalkyl;
wherein R 3 and R 4 are both H or both C 1-2 alkyl;
W is —NH 2 , halo, —OH, —NHC(O)R, —CO 2 R;
X is —S—, —O— or —NR 22 —;
Y is —H;
Z is —CH— or —N—;
each R 11 is independently —C(O)R″ or —CH 2 OC(O)R″;
R 22 is H;
each R is independently C 1-7 straight-chain alkyl or C 3-7 branched alkyl;
R″ is C 1-7 straight-chain alkyl or C 3-7 branched alkyl;
with the proviso that when R 2 is —CH 2 C 6 H 5 , R 8 is —C(R 3 )(R 4 )H or lower cycloalkyl; and
with the proviso that when R 6 is NH 2 , R 2 is,
or C 2-5 straight chain alkyl;
or R 8 is not —CH 2 C 6 H 5 .
18. A compound according to claim 17 ,
wherein R 2 is
and
X is —O— or —S—.
19. A compound according to claim 17 , wherein R 2 is C 2-5 straight-chain alkyl.
20. A compound according to claim 17 , wherein R 8 is —C(R 3 )(R 4 )H, lower cycloalkyl or H.
21. A compound according to claim 17 , wherein R 8 is —CH 2 C 6 H 5 .
22. A compound according to claim 17 , wherein R 11 is —CH 2 OC(O)C(CH 3 ) 3 .
23. A compound according to claim 17 , wherein R″ is —C(CH 3 ) 3 , —CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , or —CH 2 CH(CH 3 ) 2 .
24. A compound selected from
25. A compound of formula
26. A compound selected from: